CN112326602B - Screening method of nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal treatment and application thereof - Google Patents
Screening method of nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal treatment and application thereof Download PDFInfo
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- CN112326602B CN112326602B CN202011102461.1A CN202011102461A CN112326602B CN 112326602 B CN112326602 B CN 112326602B CN 202011102461 A CN202011102461 A CN 202011102461A CN 112326602 B CN112326602 B CN 112326602B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N2021/3129—Determining multicomponents by multiwavelength light
Abstract
A screening method of nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal treatment and application thereof. The invention belongs to the field of medicine. The invention aims to solve the technical problem that the existing contrast agent adopted in tumor diagnosis and process treatment based on optical technology is not universal. Firstly, selecting metal nano materials with different sizes, comparing absorption curves with scattering curves, observing whether one of the scattering curve sections in a first optical window is more than the absorption curve section, and simultaneously, if so, executing a second step, and if not, repeating the first step, wherein the other scattering curve section in a second optical window is less than the absorption curve section or the opposite result to the above conditions; 2. and (3) calculating an absorption and scattering characteristic spectrogram of the impurity, observing whether the condition same as that of the metal nano material is met, if so, finishing screening to obtain a nano compound, and if not, repeating the step (I).
Description
Technical Field
The invention belongs to the field of medicine, and in particular relates to a screening method of a nano-composite capable of realizing dual functions of optical diagnosis and photothermal treatment of tumors and application thereof.
Background
In recent years, optical imaging-guided photothermal treatment of tumors has received increasing attention as a tumor replacement therapy. The technology mainly utilizes specific targeting nano particles or other diagnosis and treatment agents to gather in a tumor area, so that light energy is converted into heat energy more efficiently, the temperature of the tumor area is increased, cancer cells are killed, and meanwhile, stronger light or sound signals are provided for improving the contrast of the tumor area in the imaging process. This is of great importance for improving the therapeutic effect and accuracy. Therefore, how to design and develop tumor diagnosis and treatment agents is the focus of the current tumor photothermal diagnosis and treatment process.
For nano-diagnosis and treatment agents, a higher photothermal conversion capability is required to improve the targeted thermal effect during tumor hyperthermia, and a higher optical scattering capability is required to be used as a contrast agent to improve the imaging contrast and high resolution of a specific area during diagnosis (such as optical imaging). However, current research on agents in the diagnosis and treatment process is mainly focused on nano-particles of complex shape and materials, and how to develop simple and effective tumor photothermal agents still faces challenges.
Disclosure of Invention
The invention aims to solve the technical problem that the existing contrast agent adopted in the tumor diagnosis and process treatment based on the optical technology is not universal, and provides a screening method of a nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal treatment and application thereof.
The screening method of the nano-composite capable of realizing the dual functions of tumor optical diagnosis and photothermal therapy comprises the following steps:
step one, arbitrarily selecting two metal nano materials with different sizes, wherein the shapes of the two selected metal nano materials cannot be the same, calculating an absorption and scattering characteristic spectrogram of the selected metal nano material, respectively comparing absorption curves and scattering curves in the absorption and scattering characteristic spectrogram corresponding to the two metal nano materials, and observing whether the absorption curves and the scattering curves of the two metal nano materials meet one of the following two conditions:
(1): wherein the scattering curve section of one metal nanomaterial in the first optical window is larger than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is smaller than the absorption curve section;
(2): wherein the scattering curve section of one metal nanomaterial in the first optical window is smaller than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is larger than the absorption curve section;
if yes, executing the second step, if not, repeating the first step, and re-selecting the materials for verification until the conditions are met;
and step two, calculating an absorption and scattering characteristic spectrogram of the impurities in the two metal nano materials selected in the step one on the basis of the step one, observing whether the absorption curve and the scattering curve of the impurities meet the same conditions as those of the metal nano materials selected in the step one, if so, completing screening to obtain a nano composite capable of realizing dual functions of optical diagnosis and photothermal treatment of tumors, and if not, repeating the step one.
Further limiting, in the first step, the absorption and scattering characteristic spectrogram of the selected metal nano material is calculated through DDA software under the wavelength of 700 nm-1400 nm.
Further defined, in the first step, the size radius of the metal nanomaterial is 20 nm-100 nm.
Further defined, in the first step, the metal nanomaterial is in the form of metal nanosphere particles, dimers of metal nanosphere particles, trimers of metal nanosphere particles, or tetramers of metal nanosphere particles.
Further defined, in the first step, the metal nanomaterial is gold, silver, or platinum.
Further defined, in the first step, the wavelength range of the first optical window is 750nm to 900nm.
Further defined, in the first step, the wavelength range of the second optical window is 1000nm to 1400nm.
Further defined, the impurity in the second step refers to a component of the metal nanomaterial selected in the first step that is different from the selected morphology.
And further limiting, in the second step, calculating an absorption and scattering characteristic spectrum of the impurity at a wavelength of 700 nm-1400 nm by using DDA software.
The nano-composite obtained by screening by the screening method is used as a diagnosis and treatment agent for optical diagnosis and photothermal treatment of tumors.
Further defined, the preparation method of the diagnosis and treatment agent is prepared according to the existing method, and comprises the following specific steps:
(1) Preparing the screened metal nanosphere particles into single-particle-diameter nanoparticle solution with the required particle diameter by a seed growth method;
(2) Preparing the polymer of the screened metal nanosphere particles by a seed growth method to obtain a single-particle-diameter nanoparticle solution, and then adding single-stranded and double-stranded DNA (deoxyribonucleic acid) with specific length to obtain a nanoparticle polymer solution with the required particle diameter;
(3) And (3) mixing the single-particle-diameter nanoparticle solution obtained in the step (1) with the nanoparticle polymer solution obtained in the step (2) to obtain the diagnosis and treatment agent.
Further defined, the seed growth method is a process of generating seed particles by a strong reducing agent and then generating a single-particle-size nanoparticle solution under the action of a weak reducing agent.
Further, in diagnosis, the laser wavelength used in imaging is a wavelength range having a scattering cross section > an absorption cross section, and in treatment, the laser wavelength used is a wavelength range having an absorption cross section > a scattering cross section.
Compared with the prior art, the invention has the advantages that:
1) According to the invention, the nanoparticle aggregate is mixed with a single nanoparticle solution by utilizing the difference of spectral absorption and scattering characteristics of the single nanoparticle and the nanoparticle aggregate, so that the nanoparticle aggregate is used as a novel efficient nanocomposite diagnosis and treatment agent. The agent can realize strong scattering and weak absorption characteristics in a first optical window (NIR-I, 750nm to 900 nm), thereby being used as an optical contrast agent in tumor optical imaging or diagnosis process. And in the second optical window (NIR-II, 1000nm to 1400 nm) strong absorption, weak scattering properties are achieved, thereby increasing the temperature of the tumor region as a thermal contrast agent during photothermal treatment of the tumor. On the basis, the influence of impurities contained in the nano-composite diagnosis and treatment agent is eliminated, and finally the nano-composite diagnosis and treatment agent consisting of the mixture of nano-particles with two different particle sizes and different agglomeration forms is obtained.
2) The invention can be applied to the optical imaging guided tumor photothermal treatment process, can simultaneously improve imaging definition and temperature of a tumor targeting area, and solves the problem that the optical characteristic requirements of contrast agent required by optical imaging and thermal contrast agent required by photothermal treatment are conflicting by adopting wavelengths in two different optical windows as laser wavelengths for imaging and treatment respectively.
Drawings
FIG. 1 is a graph showing absorption and scattering spectra of dimers of Au nanosphere particles having a radius of 80 and nm and Au nanosphere particles having a radius of 30 and nm in a first embodiment;
FIG. 2 is an absorption scattering spectrum of a single Au nanosphere particle, dimer, trimer and tetramer of Au nanosphere particles with a radius of 30 nm;
FIG. 3 is an absorption-scattering spectrum of a dimer of Au nanosphere particles with a radius of 80 nm.
Detailed Description
The first embodiment is as follows: the screening method of the nano-composite capable of realizing the dual functions of tumor optical diagnosis and photothermal therapy in the embodiment comprises the following steps:
step one, selecting dimers of Au nanosphere particles with the radius of 80nm and Au nanosphere particles with the radius of 30nm, calculating absorption and scattering characteristic spectrograms (see figure 1) of the Au nanosphere particles with the radius of 80nm and the Au nanosphere particles with the radius of 30nm by DDA software at the wavelength of 700 nm-1400 nm, respectively comparing the absorption curve and the scattering curve of the Au nanosphere particles with the radius of 80nm and the absorption curve and the scattering curve of the dimer of the Au nanosphere particles with the radius of 30, and observing whether the absorption curve and the scattering curve of the two metal nanomaterials meet one of the following two conditions:
(1): wherein the scattering curve section of one metal nanomaterial in the first optical window is larger than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is smaller than the absorption curve section;
(2): wherein the scattering curve section of one metal nanomaterial in the first optical window is smaller than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is larger than the absorption curve section;
the observation shows that the condition (1) is satisfied, and the second step is executed;
and step two, on the basis of the step one, calculating absorption and scattering characteristic spectrograms (see fig. 2-3) of impurities (a nano-sphere particle with the radius of 30nm, a trimer with the radius of 30nm, a tetramer and a dimer with the radius of 80 nm) in the two metal nano-materials selected in the step one under the wavelength of 700-1400 nm by DDA software, observing whether absorption curves and scattering curves of the impurities meet the same conditions as those of the metal nano-materials selected in the step one, and observing that the conditions (1) are met, and completing screening to obtain the nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal therapy.
The second embodiment is as follows: the method for preparing the diagnosis and treatment agent by utilizing the nanocomposite which is obtained by screening in the first embodiment and can realize the dual functions of tumor optical diagnosis and photothermal treatment comprises the following steps:
(1) Preparing single-particle-diameter nanoparticle solution with the particle diameter of 80nm from the Au nanosphere particles screened in the first embodiment by a seed growth method; the seed growth method comprises the steps of firstly generating seed particles through a strong reducing agent, and then generating single-particle-diameter nanoparticle solution under the action of a weak reducing agent;
(2) Preparing the dimer of the Au nanosphere particles screened in the first embodiment into a single-particle-diameter nanoparticle solution by a seed growth method, and then adding single-stranded and double-stranded DNA with specific length to obtain a nanoparticle dimer solution with the particle diameter of 30 nm; the seed growth method comprises the steps of firstly generating seed particles through a strong reducing agent, and then generating single-particle-diameter nanoparticle solution under the action of a weak reducing agent;
(3) And (3) mixing the single-particle-diameter nanoparticle solution obtained in the step (1) with the nanoparticle polymer solution obtained in the step (2) to obtain the diagnosis and treatment agent.
When the diagnostic reagent of the present embodiment is used, the laser beam required for imaging uses a wavelength region having a scattering cross section > an absorption cross section during diagnosis, and the laser beam required for treatment uses a wavelength region having an absorption cross section > a scattering cross section.
Claims (7)
1. A screening method of a nano-composite capable of realizing dual functions of tumor optical diagnosis and photothermal therapy is characterized by comprising the following steps:
step one, arbitrarily selecting two metal nano materials with different sizes, wherein the shapes of the two selected metal nano materials cannot be the same, calculating an absorption and scattering characteristic spectrogram of the selected metal nano material, respectively comparing absorption curves and scattering curves in the absorption and scattering characteristic spectrogram corresponding to the two metal nano materials, and observing whether the absorption curves and the scattering curves of the two metal nano materials simultaneously meet one of the following two conditions:
(1): wherein the scattering curve section of one metal nanomaterial in the first optical window is larger than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is smaller than the absorption curve section;
(2): wherein the scattering curve section of one metal nanomaterial in the first optical window is smaller than the absorption curve section, and the scattering curve section of the other metal nanomaterial in the second optical window is larger than the absorption curve section;
if yes, executing the second step, if not, repeating the first step, and re-selecting the materials for verification until the conditions are met;
and step two, calculating an absorption and scattering characteristic spectrogram of the impurities in the two metal nano materials selected in the step one on the basis of the step one, observing whether the absorption curve and the scattering curve of the impurities meet the same conditions as those of the metal nano materials selected in the step one, if so, completing screening to obtain a nano composite capable of realizing dual functions of optical diagnosis and photothermal treatment of tumors, and if not, repeating the step one.
2. The method for screening the nanocomposite capable of realizing dual functions of optical diagnosis and photothermal therapy of tumor according to claim 1, wherein in the first step, absorption and scattering characteristic spectrograms of the selected metal nanomaterial are calculated by DDA software at a wavelength of 700nm to 1400nm.
3. The method for screening a nanocomposite for dual functions of optical diagnosis and photothermal therapy of tumor according to claim 1, wherein the radius of dimension of the metal nanomaterial in the first step is 20nm to 100nm.
4. The method for screening a nanocomposite for dual functions of optical diagnosis and photothermal therapy of tumor according to claim 1, wherein the morphology of the metal nanomaterial in the first step is metal nanosphere particles, dimers of metal nanosphere particles, trimers of metal nanosphere particles, or tetramers of metal nanosphere particles.
5. The method for screening a nanocomposite for dual functions of optical diagnosis and photothermal therapy of tumor according to claim 4, wherein the metal nanomaterial is gold, silver or platinum.
6. The method for screening a nanocomposite capable of performing dual functions of optical diagnosis and photothermal therapy of tumor according to claim 1, wherein a wavelength interval of the first optical window in the step one is 750nm to 900nm, and a wavelength interval of the second optical window in the step one is 1000nm to 1400nm.
7. The screening method of the nanocomposite capable of realizing dual functions of optical diagnosis and photothermal therapy of tumors according to claim 1, wherein in the second step, absorption and scattering characteristic spectrograms of impurities are calculated by DDA software at a wavelength of 700 nm-1400 nm.
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| US20050250094A1 (en) * | 2003-05-30 | 2005-11-10 | Nanosphere, Inc. | Method for detecting analytes based on evanescent illumination and scatter-based detection of nanoparticle probe complexes |
| US20080268548A1 (en) * | 2006-04-03 | 2008-10-30 | Nano Chocolate Lab, Inc. | Enhancing Raman spectrographic sensitivity by using solvent extraction of vapor or particulate trace materials, improved surface scatter from nano-structures on nano-particles, and volumetric integration of the Raman scatter from the nano-particles' surfaces |
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