CN112143499A - Diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, preparation method and application thereof - Google Patents
Diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, which is a carbonyl iron-loaded mesoporous polydopamine-coated rare earth luminescent nano composite material, takes UCNPs (crown plus minus plus5(ii) a The luminescent nanoparticles have the up-conversion luminescence UCL imaging characteristic, the polydopamine has the characteristics of photoacoustic PA imaging and CO synergistic release, and the polydopamine has the PTT effect characteristic. The invention also discloses a preparation method and application thereof. Under the excitation of NIR laser, the up-conversion emission of UCNPs is transferred to carbonyl iron through fluorescence resonance energy, carbon monoxide CO is released to inhibit the growth of tumors, meanwhile, the luminescent nanoparticles are used for up-conversion luminescence imaging and the poly-dopamine is used for photoacoustic imaging, and the up-conversion luminescence imaging and the photoacoustic imaging are cooperated with CO gas therapy and the PTT effect of the poly-dopamine to serve as a diagnosis and treatment agent, so that diagnosis and treatment integration is realized.
Description
Technical Field
The invention relates to the technical field of nano biological materials, in particular to a preparation method and application of a diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent.
Background
Cancer is one of the diseases considered to be the most fatal nowadays, and has been regarded as a major threat to human life. The most mature methods in clinic are surgery, chemotherapy and radiotherapy, but these methods have their limitations, such as the surgery cannot remove all cancer cells in human body, and chemotherapy and radiotherapy have strong side effects on human body.
Photothermal therapy (PTT) is a new treatment for cancer in recent years, and its principle is to use a light absorber to absorb the energy of light and then convert it into heat, resulting in ablation of cancer cells and finally cell death. An ideal photothermal material should exhibit good absorption capacity in the near infrared region because tissue absorption is small in the near infrared region, and thus damage to biological tissues is small, while good absorption capacity can bring about high photothermal conversion efficiency, which can greatly improve the effect of photothermal therapy. However, materials with good photothermal effects generally do not have good biocompatibility, which limits the applications of such photothermal materials to biology.
Also, Gas Therapy (GT) has attracted considerable attention as a method of treating diseases using gas. The advantage of gas therapy is that, unlike chemotherapy, the molecules used for gas therapy do not develop resistance to drugs and, as an endogenous molecular signaling molecule, the gas used plays an important role in biological processes. Therefore, how to deliver the gas to the part needing treatment is an urgent problem to be solved.
For cancer detection, fluorescence imaging is unique among many imaging means due to its high sensitivity and no damage to biological tissues. Rare earth doped up-conversion luminescent nanomaterials (UCNPs) attract a lot of attention as a representative fluorescent material, because it is usually excited by low-energy light (usually near infrared light of 980nm or 808 nm) to emit high-energy light in the ultraviolet-visible light region, which can eliminate background fluorescence interference of biological tissues, and is very suitable for cell imaging and small animal living body imaging in the biological field.
Therefore, it is necessary to develop a multi-mode nano diagnosis and treatment agent integrating diagnosis and treatment, but the current diagnosis and treatment agent integrating qi therapy, photothermal therapy and fluorescence imaging cannot meet the medical requirements at present.
However, as the functional requirements of the materials increase, the difficulty of developing the composite materials also increases greatly. Due to the mutual exclusion of the characteristics of the components of the material, complex structural design, complex preparation method and other various limitations, the current multimode nano diagnosis and treatment agent integrating diagnosis and treatment is not developed.
Disclosure of Invention
The invention aims to provide a rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment, aiming at the defects in the prior art, and the rare earth luminescent nano diagnosis and treatment agent is used for realizing the integration of diagnosis and treatment, namely the integration of fluorescence imaging, gas treatment and photothermal therapy.
The invention also aims to provide a preparation method and application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent.
The invention overcomes the limitation of the prior art through research and development, and provides a diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, which adopts unique material structure, components and preparation process to realize the diagnosis and treatment (fluorescence imaging) of diseases such as cancer and the like, and combines with multi-mode treatment, so that the diagnosis and treatment integrated agent can be applied to the diagnosis and treatment integrated technology, and particularly has very obvious diagnosis and treatment effects on the synergetic gas treatment and photothermal physiotherapy of cancer.
In order to achieve the purpose, the invention adopts the technical scheme that:
the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the diagnosis and treatment integrated rare earth luminescent nano composite material is coated by mesoporous polydopamine loaded with carbonyl iron, UCNPs (crown plus minus plus5(ii) a The luminescent nanoparticles in the composite material have the imaging characteristic of up-conversion luminescence UCL, the poly-dopamine has the characteristics of photoacoustic PA imaging and CO synergistic release, and the poly-dopamine has the PTT effect characteristic; under the excitation of near infrared light (NIR) laser, the up-conversion emission of UCNPs is transferred to carbonyl iron through Fluorescence Resonance Energy Transfer (FRET), carbon monoxide (carbon monoxide) is released to inhibit the growth of tumors, meanwhile, the up-conversion luminescence UCL imaging is carried out on the luminescent nanoparticles, the photoacoustic PA imaging is carried out on polydopamine, and the up-conversion luminescence UCL imaging and the PTT effect of the polydopamine of CO are cooperated with each other to serve as a diagnosis and treatment agent, so that the diagnosis and treatment integration is realized.
The oil-soluble rare earth up-conversion luminescent nanoparticle comprises: NaYF4:Yb,Tm、NaYF4:Yb,Tm,Er、NaYF4:Yb,Tm@NaGdF4、NaYF4:Yb,Tm@NaYF4、NaYF4:Yb,Tm@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaGdF4、NaYF4:Yb,Tm,Er@NaYF4One or more of (a).
The wavelength of the near infrared NIR laser is 808 +/-5 nanometers or 980 +/-5 nanometers.
The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized by comprising the following steps:
taking oil-soluble rare earth up-conversion luminescent nano-particles UCNPs as cores, and polymerizing dopamine DA on the surfaces of the luminescent nano-particles by using an inverse microemulsion method to form a polydopamine PDA-coated luminescent nano-composite material; removing the template agent to obtain the mesoporous polydopamine mPDA coated rare earth luminescent nano composite material, and then carrying out the chelation between the rich catechol structure of the mPDA layer and iron ions to load carbonyl iron Fe (CO)5And obtaining the carbonyl iron-loaded mesoporous polydopamine-coated rare earth luminescent nano composite material.
The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized by comprising the following steps:
(1) preparing a set amount of Cetyl Trimethyl Ammonium Chloride (CTAC) clear solution, dropwise adding a cyclohexane dispersion liquid of quantitative oil-soluble rare earth up-conversion luminescent nanoparticles into the CTAC solution, and violently stirring to obtain a modified UCNPs dispersion liquid; preparing a dopamine aqueous solution, dropwise adding the dopamine aqueous solution into the modified UCNPs dispersion liquid, then adding ammonia water, violently stirring, and centrifuging, washing and dispersing a product to obtain a first dispersion liquid;
(2) preparing an ethanol solution of carbonyl iron, adding the ethanol solution of carbonyl iron into the first dispersion liquid, stirring, and centrifuging, washing and dispersing the obtained product to obtain a second dispersion liquid; preparing an ethanol solution of polyethylene glycol, mixing the ethanol solution of polyethylene glycol with the second dispersion liquid, stirring, centrifuging, washing and dispersing the product to obtain the final diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent.
The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the steps (1) and (2) specifically comprise the following steps:
(1) preparation of CTAC solution: weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, dropwise adding the prepared cyclohexane dispersion liquid of quantitative oil-soluble rare earth up-conversion luminescent nanoparticles into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing in ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing an obtained product with deionized water, and finally dispersing in the deionized water to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
The application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the diagnosis and treatment agent is used for carbon monoxide gas treatment, photothermal treatment and multi-mode diagnosis of UCL and PA.
The application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that when the diagnosis and treatment agent is used for carbon monoxide gas therapy, the up-conversion luminescence of UCNPs is transferred to carbonyl iron by FRET under the irradiation of near infrared NIR laser, CO is released under the coordination of polydopamine, and the growth of tumors is inhibited.
The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is used for photo-thermal treatment, mPDA absorbs energy of laser and converts the energy into heat energy under the irradiation of near infrared NIR laser, and the temperature of the surrounding environment is raised through the photo-thermal effect, so that the photo-thermal treatment PTT effect is realized.
The application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the rare earth luminescent nano diagnosis and treatment agent is used as a raw material to further prepare a photoacoustic imaging contrast agent in the diagnosis and treatment agent.
The invention has the advantages that:
(1) the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the invention realizes the purpose of using fluorescence imaging for cancer diagnosis, and is combined with treatment means such as gas therapy, photothermal therapy and the like, so that the effect of developing the diagnosis and treatment integrated nano diagnosis and treatment agent is achieved. The modification material adopted by the invention is mesoporous polydopamine, has a unique structure, stable chemical properties and good biocompatibility, has a good photo-thermal effect, and can be used as a photo-thermal therapeutic agent. Meanwhile, the loaded carbonyl iron can absorb blue light and ultraviolet light emitted by the rare earth up-conversion nanoparticles, and CO is released under the coordination of polydopamine.
In the prior art, the coating layer used as a loaded drug can not provide other functional functions, and the biocompatibility and the like of the coating layer can not meet the requirements of biological application. Through the improvement of the structure and the process, the adopted mesoporous polydopamine layer has excellent biocompatibility and water solubility and can provide the function of photothermal therapy except for drug loading. Meanwhile, the loaded carbonyl iron can absorb the emission of ultraviolet and blue light regions of the up-conversion nanoparticles, and CO is released under the coordination of the polydopamine, so that the endogenous gas molecules can achieve the treatment effect, and achieve the synergistic treatment effect together with the mesoporous polydopamine layer.
(2) The preparation method provided by the invention has the advantages of simple process, convenient preparation and low cost, and adopts an inverse microemulsion method, wherein the oil-soluble up-conversion luminescent nanoparticles are modified into water-soluble particles by dopamine, and then the template agent is removed to obtain mesoporous polydopamine-coated up-conversion luminescent nanoparticles; under room temperature, carbonyl iron is loaded in the pore canal and on the surface of the polydopamine through the strong chelation of the catechol structure on the polydopamine and the iron, and the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent with the synergistic effect of gas therapy and photothermal physiotherapy is obtained. The preparation method simultaneously considers the synergy of the component characteristics, the structure and the efficacy of the material, finally synthesizes the excellent nano diagnosis and treatment agent integrating gas collection therapy, photothermal therapy and fluorescence imaging, and is also beneficial to promoting the development of medical technology and reducing the medical cost.
(3) According to the preparation method provided by the invention, a layer of polydopamine is coated on the surface of the oil-soluble up-conversion nanoparticles by a reverse micro-emulsion method at room temperature, then the mesoporous polydopamine-coated up-conversion nanoparticles are obtained by removing a template agent, carbonyl iron is loaded by the strong chelation of a catechol structure rich in the surface of the polydopamine and iron ions, and then the carbonyl iron is modified by polyethylene glycol to obtain the final diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent. The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the invention has the advantages of few process steps, efficient and stable preparation process, high repeatability and easiness in industrialization, and the prepared product has compatible characteristics, uniform size, stable performance and good consistency.
(4) The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the invention can be applied to fluorescence imaging, photothermal therapy and qi therapy through a unique core-shell structure and the interaction of UCNPs and carbonyl iron, so that the diagnosis and treatment integration is realized. Under the irradiation of 980 or 808nm laser, the up-conversion emission of UCNPs is absorbed by carbonyl iron, so that CO is released to achieve the effect of gas treatment, and meanwhile, the mesoporous polydopamine layer can absorb energy of the laser to generate photo-heat, so that the effect of photo-heat treatment is achieved.
(5) The application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the invention has the multifunctional application of fluorescence imaging, gas treatment and photothermal physiotherapy, and can be used for realizing integration of targeted diagnosis and multi-mode treatment.
(6) According to the diagnosis and treatment agent and the preparation method thereof provided by the invention, the modification material adopts the mesoporous polydopamine, and under the coordination of other components and preparation processes, the mesoporous polydopamine has good biocompatibility and higher photothermal conversion efficiency, and becomes a high-efficiency photothermal conversion agent.
(7) The nano composite material prepared by the diagnosis and treatment agent and the preparation method thereof provided by the invention has the advantages of uniform size, good stability and good biocompatibility, has the functions of photothermal therapy and gas therapy, can be applied to the fields of up-conversion fluorescence imaging, treatment and the like, and meets the requirement of clinical diagnosis and treatment integration.
To more clearly explain the structural features and effects of the present invention, the following detailed description is given with reference to the accompanying drawings and specific embodiments.
Drawings
FIG. 1 is a fluorescence spectrum of a rare earth luminescent nano diagnostic agent in example 1 of the present invention;
FIG. 2 is a TEM photograph of a rare earth luminescent nano-diagnostic agent in example 1 of the present invention;
FIG. 3 is a graph showing the ultraviolet absorption spectrum of a rare earth luminescent nano diagnostic agent mixed with myoglobin under 980nm laser irradiation in example 1 of the present invention;
fig. 4 is a photo-thermal image of the rare earth luminescent nano-diagnostic agent irradiated by 808nm laser at different concentrations according to embodiment 1 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Referring to the attached drawings, the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment of the invention is a carbonyl iron-loaded mesoporous polydopamine-coated rare earth luminescent nano composite material, oil-soluble rare earth up-conversion luminescent nano particles UCNPs are taken as cores, polydopamine PDA is polymerized on the surfaces of the luminescent nano particles and coats the UCNPs particles to form a shell, and carbonyl iron Fe (CO) is loaded in the shell5(ii) a Carbonyl iron is loaded on the pore canal and the surface of the shell mesoporous polydopamine; the luminescent nanoparticles in the composite material have the imaging characteristic of up-conversion luminescence UCL, the poly-dopamine has the characteristics of photoacoustic PA imaging and CO synergistic release, and the poly-dopamine has the PTT effect characteristic; the composite material is excited by Near Infrared (NIR) laser, UCNPs are subjected to up-conversion emission and pass through fluorescenceThe resonance energy transfer FRET is transferred to carbonyl iron, carbon monoxide CO is released under the coordination of polydopamine, the growth of tumors is inhibited, meanwhile, the luminescent nanoparticles are subjected to up-conversion luminescence UCL imaging and the polydopamine is subjected to photoacoustic PA imaging, and the luminescence nanoparticles are mutually coordinated with CO gas therapy GT and the PTT effect of the polydopamine to serve as a diagnosis and treatment agent, so that diagnosis and treatment integration is realized.
Wherein the oil-soluble rare earth up-conversion luminescent nanoparticles comprise: NaYF4:Yb,Tm、NaYF4:Yb,Tm,Er、NaYF4:Yb,Tm@NaGdF4、NaYF4:Yb,Tm@NaYF4、NaYF4:Yb,Tm@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaGdF4、NaYF4:Yb,Tm,Er@NaYF4One or more of (a). Specifically, one or more of the above-mentioned materials can be selected according to the requirements, and the technical effects of the invention can be achieved.
The wavelength of the near infrared NIR laser is 808 +/-5 nanometers or 980 +/-5 nanometers.
The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent adopts an inverse microemulsion method, and comprises the following steps:
taking oil-soluble rare earth up-conversion luminescent nano-particles UCNPs as cores, and polymerizing dopamine DA on the surfaces of the luminescent nano-particles by using an inverse microemulsion method to form a polydopamine PDA-coated luminescent nano-composite material; removing the template agent to obtain the mesoporous polydopamine mPDA coated rare earth luminescent nano composite material, and then carrying out the chelation between the rich catechol structure of the mPDA layer and iron ions to load carbonyl iron Fe (CO)5And obtaining the carbonyl iron-loaded mesoporous polydopamine-coated rare earth luminescent nano composite material.
More specifically, the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment includes the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, dropwise adding the prepared cyclohexane dispersion liquid of the quantitative oil-soluble rare earth thulium-doped up-conversion luminescent nanoparticles into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is applied as a diagnosis and treatment agent and is used for carbon monoxide gas treatment, photothermal treatment and multi-mode diagnosis of UCL and PA.
When the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is applied to carbon monoxide gas therapy, the up-conversion luminescence of UCNPs is transferred to carbonyl iron by FRET under the irradiation of near infrared NIR laser, CO is released under the coordination of polydopamine, and the growth of tumors is inhibited.
The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is applied to photo-thermal treatment as a diagnosis and treatment agent, under the irradiation of Near Infrared (NIR) laser, mPDA absorbs the energy of the laser and converts the energy into heat energy, and the temperature of the surrounding environment is raised through the photo-thermal effect, so that the photo-thermal treatment PTT effect is realized.
The rare earth luminescent nano diagnosis and treatment agent integrated with diagnosis and treatment is used as a raw material to further prepare a photoacoustic imaging contrast agent in the diagnosis and treatment agent.
The diagnosis and treatment agent and the preparation method thereof provided by the embodiment of the invention comprise the steps of firstly coating Polydopamine (PDA) on the surface of rare earth luminescent nanoparticles by adopting a reverse microemulsion method, and then removing a template agent to obtain mesoporous polydopamine (mPDA) -coated rare earth luminescent nanoparticles; the polydopamine has rich catechol structure and has good chelation with iron ions, so that the carbonyl iron-loaded mesoporous polydopamine-coated rare earth luminescent nano diagnosis and treatment agent can be obtained finally. The obtained nano diagnosis and treatment agent is of a core-shell structure, the core is rare earth luminescent nano particles, the shell layer is mesoporous polydopamine, and carbonyl iron is loaded on the pore canal and the surface of the mesoporous polydopamine. The preparation method provided by the invention has the advantages of simple process, convenience in operation and the like; the product has the advantages of ingenious structure, compatible characteristics, multiple functions, uniform size, good stability and good biocompatibility, simultaneously has the functions of carbon monoxide Gas Therapy (GT) and photothermal therapy (PTT), has the function of diagnosis and treatment integration, and can be used as a diagnosis and treatment agent for photoacoustic imaging (PA) and up-conversion luminescence imaging (UCL) guided cancer gas therapy and photothermal therapy.
FIG. 1 is a fluorescence spectrum of 980nm laser-excited rare earth luminescent nano diagnosis and treatment agent integrated with diagnosis and treatment prepared in example 1 of the present invention, from which emission peaks at 365nm and 475nm, corresponding to Tm, can be observed3+Is/are as follows1D2/1G4→3H6And are and1I6/1D2→3F4and the transition is carried out, and 980nm is just positioned at an optical window of a biological tissue, so that the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent still keeps good up-conversion fluorescence property and is very suitable for cell and small animal living body imaging. Meanwhile, the absorption of carbonyl iron and the emission of UCNPs have good overlap, so that the characteristic synergy that the carbonyl iron can absorb the up-conversion light and release CO under the excitation of 980nm is realized.
Example 2:
the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, the preparation method and the application thereof provided by the embodiment are basically the same as those of the embodiment 1, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, dropwise adding the prepared cyclohexane dispersion liquid of the quantitative oil-soluble rare earth erbium and thulium co-doped up-conversion luminescent nanoparticles into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Fig. 2 is a TEM photograph of the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment obtained in example 2 of the present invention, and it can be seen from the drawing that the mesoporous poly dopamine layer is uniformly coated around the upconversion nanoparticles, which indicates that the method can effectively obtain the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent with characteristics of synergy, dispersed morphology and uniform coating, and the average particle size of the nano material is about 25-30 nm, because the small-sized nanoparticles are more easily endocytosed by cells, which is beneficial to circulation in the living body, and is of great significance for the application of the small-sized nanoparticles in biological imaging and treatment.
Example 3:
the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, the preparation method and the application thereof provided by the embodiment are basically the same as those of the embodiments 1 and 2, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of CTAC, and removingIn the son water, the prepared quantitative oil-soluble rare earth thulium is doped with inert NaGdF4Dropwise adding the cyclohexane dispersion liquid of the up-conversion luminescent nanoparticles of the shell layer into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Fig. 3 is an ultraviolet-visible absorption spectrum of myoglobin (Mb) and rare earth luminescent nano diagnostic agent integrated with diagnosis under 980nm laser irradiation, and it can be seen that with the increase of laser irradiation time, the absorption peak of myoglobin at 430nm is decreased, and the characteristic absorption peak corresponding to myoglobin combined with CO at 410nm is increased, which shows that with the irradiation of 980nm laser, the rare earth luminescent nano diagnostic agent integrated with diagnosis can release CO, thereby providing a foundation for the composite material to achieve the effect of gas therapy.
Example 4:
the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent, the preparation method and the application thereof provided by the embodiment are basically the same as those of the embodiments 1, 2 and 3, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, and dissolving the prepared quantitative oilRare earth thulium doped inert NaYF cladding4Dropwise adding the cyclohexane dispersion liquid of the up-conversion luminescent nanoparticles of the shell layer into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
FIG. 4 is a photo-thermal image of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent with different concentrations under the excitation of 808nm laser, and it can be seen that the material is 1.5W/cm under the 808nm laser2The power density of the material is low, the photo-thermal effect is good, and the temperature rise can reach 25 ℃ under the highest material concentration.
Example 5:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as the embodiments 1 to 4, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving the CTAC in 20-40 mL of deionized water, and then coating the prepared quantitative oil-soluble rare earth erbium and thulium co-doped with inert NaGdF4Dropwise adding the cyclohexane dispersion liquid of the up-conversion luminescent nanoparticles of the shell layer into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized waterDropwise adding the mixture into high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution quickly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing the product into ethanol to obtain first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Example 6:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as the embodiments 1 to 5, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving the CTAC in 20-40 mL of deionized water, and then coating the prepared quantitative oil-soluble rare earth erbium and thulium co-doped with inert NaYF4Dropwise adding the cyclohexane dispersion liquid of the up-conversion luminescent nanoparticles of the shell layer into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Example 7:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as the embodiments 1 to 6, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, and coating the prepared quantitative oil-soluble rare earth thulium with NaYF4Dropwise adding cyclohexane dispersion liquid of up-conversion luminescent nanoparticles of Nd and Yb shells into a dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Example 8:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as the embodiments 1 to 7, and the difference is that the preparation method comprises the following steps:
(1)preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, and coating the prepared quantitative oil-soluble rare earth thulium with NaGdF4Dropwise adding cyclohexane dispersion liquid of up-conversion luminescent nanoparticles of Nd and Yb shells into a dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Example 9:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as that of the embodiments 1 to 8, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving the CTAC in 20-40 mL of deionized water, and coating the prepared quantitative oil-soluble rare earth erbium and thulium co-doped with NaGdF4Dropwise adding cyclohexane dispersion liquid of up-conversion luminescent nanoparticles of Nd and Yb shells into a dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 h, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 h, and using the obtained productWashing with ethanol and deionized water, and dispersing in ethanol to obtain a first dispersion;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
Example 10:
the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment is basically the same as the preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent provided by the embodiment 1 to 9, and the difference is that the preparation method comprises the following steps:
(1) preparing a CTAC solution, weighing 0.1-0.2 g of CTAC, dissolving the CTAC in 20-40 mL of deionized water, and coating the prepared quantitative oil-soluble rare earth erbium and thulium with NaYF4Dropwise adding cyclohexane dispersion liquid of up-conversion luminescent nanoparticles of Nd and Yb shells into a dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing into ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing the obtained product with deionized water, and finally dispersing in deionized water in a dark place to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
The invention is characterized in that the composite material is prepared by adopting an inverse microemulsion method, and specifically, Dopamine (DA) is polymerized on the surface of an up-conversion luminescent nano particle by using the inverse microemulsion method to form the up-conversion luminescent nano composite material wrapped by Polydopamine (PDA); removing template agent to obtain mesoporous polydopamine (mPDA) -coated up-conversion luminescence nano composite material, and loading carbonyl iron (Fe (CO))5) Obtaining carbonyl iron loaded mPDA coated rare earth luminescent nano diagnosis and treatment agent; under the excitation of near infrared light (NIR), the up-conversion emission of UCNPs is transferred to carbonyl iron through Fluorescence Resonance Energy Transfer (FRET), carbon monoxide (CO) is released, the growth of tumors is inhibited, meanwhile, the polydopamine layer has a good photo-thermal effect, and under the irradiation of NIR, the ambient environment is heated, so that a good photo-thermal treatment (PTT) effect is obtained. In addition, the upconversion luminescence imaging (UCL) and the photoacoustic imaging (PA) of the polydopamine of the upconversion nanoparticles are mutually cooperated with the CO Gas Therapy (GT) and the PTT of the polydopamine, so that diagnosis and treatment integration is realized.
The present invention is not limited to the above embodiments, and other mesoporous polydopamine-coated upconversion luminescent nanoparticies and therapeutics obtained by the same or similar method and the preparation method thereof, such as upconversion nanocrystals (NaYF) doped with different rare earth ions4:Yb,Tm NaGdF4:Yb,Tm；NaLuF4Yb, Tm, etc.), different organic ligands for modifying the oil-soluble up-converting nanoparticles, different structures of the drug for phototherapy, etc., are within the scope of the present invention.
Claims (10)
1. The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent is characterized in that the diagnosis and treatment integrated rare earth luminescent nano composite material is coated by mesoporous polydopamine loaded with carbonyl iron, UCNPs (crown plus minus plus5(ii) a Luminescent nanoparticles in the compositeThe particle has the imaging characteristic of up-conversion luminescence UCL, polydopamine has the characteristics of photoacoustic PA imaging and CO synergistic release, and polydopamine has the PTT effect characteristic; under the excitation of near infrared light (NIR) laser, the up-conversion emission of UCNPs is transferred to carbonyl iron through Fluorescence Resonance Energy Transfer (FRET), carbon monoxide (carbon monoxide) is released to inhibit the growth of tumors, meanwhile, the up-conversion luminescence UCL imaging is carried out on the luminescent nanoparticles, the photoacoustic PA imaging is carried out on polydopamine, and the up-conversion luminescence UCL imaging and the PTT effect of the polydopamine of CO are cooperated with each other to serve as a diagnosis and treatment agent, so that the diagnosis and treatment integration is realized.
2. The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 1, wherein the oil-soluble rare earth up-conversion luminescent nano particles comprise: NaYF4:Yb,Tm、NaYF4:Yb,Tm,Er、NaYF4:Yb,Tm@NaGdF4、NaYF4:Yb,Tm@NaYF4、NaYF4:Yb,Tm@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaYF4:Nd,Yb、NaYF4:Yb,Tm,Er@NaGdF4、NaYF4:Yb,Tm,Er@NaYF4One or more of (a).
3. The diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 1, wherein the wavelength of the near infrared NIR laser is 808 +/-5 nm or 980 +/-5 nm.
4. The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to one of claims 1 to 3, characterized by comprising the following steps:
taking oil-soluble rare earth up-conversion luminescent nano-particles UCNPs as cores, and polymerizing dopamine DA on the surfaces of the luminescent nano-particles by using an inverse microemulsion method to form a polydopamine PDA-coated luminescent nano-composite material; removing the template agent to obtain the mesoporous polydopamine mPDA coated rare earth luminescent nano composite material, and then carrying out the chelation between the rich catechol structure of the mPDA layer and iron ions to load carbonyl iron Fe (CO)5To obtain the mesoporous loaded with carbonyl ironA polydopamine-coated rare earth luminescent nano composite material.
5. The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 4, which is characterized by comprising the following steps:
(1) preparing a set amount of Cetyl Trimethyl Ammonium Chloride (CTAC) clear solution, dropwise adding a cyclohexane dispersion liquid of quantitative oil-soluble rare earth up-conversion luminescent nanoparticles into the CTAC solution, and violently stirring to obtain a modified UCNPs dispersion liquid; preparing a dopamine aqueous solution, dropwise adding the dopamine aqueous solution into the modified UCNPs dispersion liquid, then adding ammonia water, violently stirring, and centrifuging, washing and dispersing a product to obtain a first dispersion liquid;
(2) preparing an ethanol solution of carbonyl iron, adding the ethanol solution of carbonyl iron into the first dispersion liquid, stirring, and centrifuging, washing and dispersing the obtained product to obtain a second dispersion liquid; preparing an ethanol solution of polyethylene glycol, mixing the ethanol solution of polyethylene glycol with the second dispersion liquid, stirring, centrifuging, washing and dispersing the product to obtain the final diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent.
6. The preparation method of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 5, wherein the steps (1) and (2) specifically comprise the following steps:
(1) preparation of CTAC solution: weighing 0.1-0.2 g of CTAC, dissolving in 20-40 mL of deionized water, dropwise adding the prepared cyclohexane dispersion liquid of quantitative oil-soluble rare earth up-conversion luminescent nanoparticles into the dissolved CTAC solution, and violently stirring at room temperature for 8-12 h to obtain a modified UCNPs dispersion liquid; weighing 20-80 mg of dopamine, dissolving in deionized water, dropwise adding into the high-speed stirring modified UCNPs dispersion liquid, violently stirring for 1-3 hours, then adding 100-150 mu L of ammonia water, observing that the solution rapidly becomes brownish black, continuously and violently stirring for 18-28 hours, washing the obtained product with ethanol and deionized water, and finally dispersing in ethanol to obtain a first dispersion liquid;
(2) dissolving 3-5 mL of carbonyl iron solution in 20-50 mL of ethanol, stirring uniformly in a dark place, mixing with the first dispersion liquid, stirring at room temperature in a dark place for 12-18 h, washing the obtained product with ethanol and water, and finally dispersing in ethanol in a dark place to obtain a second dispersion liquid; and (3) dispersing 0.1-0.3 g of polyethylene glycol (PEG) in 10-20 mL of ethanol, uniformly stirring, mixing with the second dispersion liquid, stirring overnight, washing an obtained product with deionized water, and finally dispersing in the deionized water to obtain the rare earth luminescent nano diagnosis and treatment agent integrating diagnosis and treatment.
7. Use of the diagnostically integrated rare earth luminescent nanopedicinal agent according to one of claims 1 to 3 as a diagnostic agent for carbon monoxide gas therapy and photothermal therapy as well as for multimodal diagnosis of UCL and PA.
8. The use of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 7, wherein when the diagnosis and treatment agent is used in carbon monoxide gas therapy, the up-conversion luminescence of UCNPs is transferred to carbonyl iron by FRET under the irradiation of near infrared NIR laser, and CO is released under the coordination of polydopamine to inhibit the growth of tumors.
9. The use of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent according to claim 7, wherein the diagnosis and treatment agent is used for photothermal therapy as a diagnosis and treatment agent, under the irradiation of near infrared NIR laser, mPDA absorbs the energy of the laser and converts the energy into heat energy, and the temperature of the surrounding environment is raised through photothermal effect, so that the photothermal therapy PTT effect is realized.
10. The application of the diagnosis and treatment integrated rare earth luminescent nano diagnosis and treatment agent as claimed in claim 7, which is characterized in that the photoacoustic imaging contrast agent in the diagnosis and treatment agent is further prepared by taking the rare earth luminescent nano diagnosis and treatment agent as a raw material.
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