CN110639015A

CN110639015A - Preparation method of chiral light-controllable oxygen-deficient molybdenum oxide nanoparticles and application of chiral light-controllable oxygen-deficient molybdenum oxide nanoparticles in tumor photothermal therapy

Info

Publication number: CN110639015A
Application number: CN201910954219.8A
Authority: CN
Inventors: 徐晓倩; 程佳吉
Original assignee: China Medical University
Current assignee: China Medical University
Priority date: 2019-10-09
Filing date: 2019-10-09
Publication date: 2020-01-03
Anticipated expiration: 2039-10-09
Also published as: CN110639015B

Abstract

The invention discloses a preparation method and application of reduced molybdenum oxide nanoparticles with controllable chiral light and targeted tumor cell photothermal therapy application. On the basis of taking molybdenum trioxide as mother liquor, a chiral enhanced double-channel oxygen-deficient molybdenum oxide nano material is innovatively obtained through a chiral induction effect; by comparing the variables such as the dosage of organic molecules, the combination mode and the like, the photo-thermal treatment reagent based on the chiral molybdenum oxide nano material is developed. The operation method is simple and convenient, and the raw materials are cheap and easy to obtain. The chiral semiconductor nano material has strong hand absorption on circularly polarized visible laser and near infrared laser respectively, and can generate high temperature to achieve the effect of photo-thermal treatment. Widens the thought for the application of the chiral nano material in the tumor photothermal therapy and reduces the cost of the cancer photothermal therapy.

Description

Preparation method of chiral light-controllable oxygen-deficient molybdenum oxide nanoparticles and application of chiral light-controllable oxygen-deficient molybdenum oxide nanoparticles in tumor photothermal therapy

Technical Field

The invention relates to the field of nano biological materials, in particular to a preparation method of chiral light-controllable oxygen-deficient molybdenum oxide nano particles and application of the chiral light-controllable oxygen-deficient molybdenum oxide nano particles in tumor photothermal therapy.

Background

The application of the nanoparticles in Photothermal therapy (PTT) is based on the characteristic that the nanoparticles can rapidly generate heat after absorbing Near-infrared light (NIR), and high temperature (hyperthermia) exceeding 40 ℃ is generated in cancer cells, so that protein in the cells is deteriorated, cell membranes are broken to cause irreversible damage to the cancer cells to kill the cancer cells, and the NIR-PTT Photothermal therapy is expected to become a tumor treatment mode taking a novel nanotechnology as a background due to strong operability and low damage of the nanoparticles. The main disadvantages of the conventional PTT treatment methods are: firstly, the material itself needs to have ultrahigh absorbance to near infrared light or use stronger laser irradiation for a longer time to provide enough energy to generate heat; ② the cancer cell killing and normal cell killing may be simultaneously and non-selectively caused by long-time strong light irradiation.

Chirality refers to the inability of an object to coincide with its mirror image. For inorganic nanomaterials, chiral optical activity may be enhanced. Plasma or exciton coupling effects in nanostructures can create new materials with super-enhanced properties. The introduction of chirality presents a new solution to the above problem. Because the chiral nanoparticles have selectivity on the absorption of incident light, if proper polarized light is selected as an irradiation light source, the absorption efficiency of the material on the incident light is greatly improved, so that the time and energy consumption required by photothermal therapy are reduced; meanwhile, because the illumination time is reduced, the number of normal cells killed by light source irradiation is reduced, and the cost of photo-thermal treatment of cancer is greatly reduced.

The non-stoichiometric oxide of the transition metal is a nano material with the advantages of wide and strong NIR absorption, large specific surface area, easy drug loading, good photo-thermal conversion effect, biocompatibility and the like. Wherein the oxygen is deficient in molybdenum oxide nano material (MoO)_3-x) Has been applied to the diagnosis and treatment of tumor due to the carrier concentration adjusted by doping or the like and the liquid property thereofMetal ion detection and other nano biomedical fields. And the chiral oxygen-deficient molybdenum oxide nano material can provide higher dimensional promotion for the application of the chiral oxygen-deficient molybdenum oxide nano material in the fields.

In recent years, the morbidity and mortality of malignant tumors are in a rapid rising trend, new materials are used, a new mechanism is a necessary trend for solving the malignant tumors, and the energy-saving chiral functional nano material with multiple dimensions becomes a hot point for research.

Disclosure of Invention

The first purpose of the invention is to provide a novel inorganic chiral semiconductor nano material, namely chiral light controllable oxygen-deficient molybdenum oxide nano particle, which can simultaneously integrate different chiral photothermal effects and is applied to PTT treatment.

The second purpose of the invention is to provide a preparation method of the novel inorganic chiral semiconductor nano material, namely the chiral light controllable oxygen deficient molybdenum oxide nano particle.

The third purpose of the invention is to provide the application of the chiral light-controllable oxygen-deficient molybdenum oxide nanoparticles in preparing tumor photothermal therapeutic agents.

In order to achieve the purpose, the invention provides the following technical scheme:

a chiral light-controllable oxygen-deficient molybdenum oxide nano material has a chemical formula of L-/D-Cys-MoO_3-xWherein X represents a difference in the degree of oxygen deficiency; according to the degree of oxygen deficiency (x value) and the chirality of the reducing agent used, L-/D-Cys-MoO can be divided_2.83(blue), L-/D-Cys-MoO_2.68(Green) and L-/D-Cys-MoO₂(brown) six different nanoparticles.

Further, the reducing agent is chiral cysteine.

Further, the value of X can be adjusted by adjusting L-/D-Cys-MoO_3-xThe dosage of the nanosheet and the reducing agent chiral cysteine molecule.

Further, the chiral light controllable oxygen-deficient molybdenum oxide nano material is most preferably blue L-/D-Cys-MoO_3-xX is 0.17; green L-/D-Cys-MoO_3-xX is 0.32; brown L-/D-Cys-MoO_3-xX is 1; i.e. L-/D-Cys-MoO_2.83Is blue, L-/D-Cys-MoO_2.68Is green and L-/D-Cys-MoO₂Is brown.

Further, the chiral optically-controllable oxygen-deficient molybdenum oxide nanomaterial can be prepared by the prior art and can have any size; the most preferred size is blue: 2.7nm, green: 2.9nm, brown: 28.7 nm.

A preparation method of a chiral light-controllable oxygen-deficient molybdenum oxide nano material comprises the following steps:

s1: mixing MoS₂Preparing the powder and deionized water into an aqueous solution, adding a certain amount of hydrogen peroxide, fully stirring and mixing for 12-24 hours, and obtaining MoO through an oxidation reaction₃An aqueous solution of (a);

s2: carrying out hydrothermal treatment on the solution prepared in the step S1 at the temperature of 60-80 ℃ for 2-4 hours, and removing redundant hydrogen peroxide to obtain a mother solution;

s3: cooling, taking the mother liquor prepared by S2, adding a certain amount of cysteine to carry out reduction reaction gradually, and obtaining the product.

A preparation method of a chiral light-controllable oxygen-deficient molybdenum oxide nano material specifically comprises the following steps:

s1: 80g of MoS₂Preparing the powder and 50ml of deionized water into an aqueous solution, adding 3.75ml of hydrogen peroxide, fully stirring and mixing for 12 hours overnight, and obtaining MoO through oxidation reaction₃An aqueous solution of (a);

s2: carrying out hydrothermal treatment on the solution prepared in the step S1 at 80 ℃ for 2 hours, and removing redundant hydrogen peroxide to obtain mother liquor;

s3: cooling, taking 1.5ml of mother liquor prepared in S2, and adding a certain amount of cysteine to gradually perform reduction reaction: (L-/D-Cys-MoO)_2.83(blue) plus 5 mg; L-/D-Cys-MoO_2.68(green) 20mg and L-/D-Cys-MoO₂Adding 60mg into the brown solution, and reducing the mixture for 4 hours at room temperature to obtain the product.

Furthermore, the addition amount of the hydrogen peroxide and the cysteine are determined by the chemical formula L-/D-Cys-MoO_3-xAnd calculating to obtain the product.

The chiral light controllable oxygen-deficient molybdenum oxide nano material is used for preparing a tumor photo-thermal therapeutic agent.

Further, the tumor cell is preferably a Hela cell or a skin cancer cell.

A tumor therapeutic agent comprises the chiral oxygen-deficient molybdenum oxide nano material and/or other effective components for tumor therapy.

The invention provides a PTT treatment mode different from the traditional near-infrared response, and introduces strong absorption and strong chirality in a visible light region while introducing chirality to a molybdenum oxide system through a Metal-ligand effect. The chirality is caused by the electron transfer effect of the metal core (molybdenum) to the surface ligand, and provides a new channel for the chiral treatment of PTT.

The preparation method of the chiral nano material provided by the invention can realize MoO₃The nano-dots are used for gradually reducing and coating the mother liquor to generate chiral molybdenum oxide nano-particles, and the target of adjusting the size, color and valence state of the molybdenum oxide nano-particles can be achieved while introducing chirality by adjusting the dosage of a reducing agent coating agent cysteine.

In the preparation method provided by the invention, MoO₃The nanodots have higher valence and are easy to reduce, and the MoO load can be regulated and controlled by changing the dosage of cysteine in the step S1 or the step T1_3-xThe amount of chiral ligand on the surface of the nanoparticle thus achieves tuning of chirality (circular dichroism).

During the synthesis process of the chiral oxygen-deficient molybdenum oxide nanoparticles, sulfur sources can be provided by using S-containing amino acids (such as L-Cys), molybdenum oxide nanoparticles with different sizes, colors and valence states can be obtained through different dosage control, and the valence states can be tracked and characterized through XPS. The amount of the chiral ligand on the surface of the nano-particle is different due to different cysteine dosage, and the difference can be subjected to spectrum analysis through Circular Dichroism (CD), so that a simple and convenient observation method is provided for the preparation of the material. In addition, the chiral introduction concept of Metal-ligand involved in the invention can also be tracked and measured by circular dichroism and ultraviolet visible spectrum, and theoretical analysis conditions are provided for the introduction mechanism of chirality.

When x is 1, i.e., hexavalent molybdenum is reduced to tetravalent, due to the coordination of the ligand at the particle surface and the strong binding of the mercapto group (-SH) to the metal molybdenum atom, charge is conducted from the molybdenum oxide core to the chiral ligand, and a new absorption in the visible region and circular dichroism are generated through the interaction of the chiral ligands. In the chiral oxygen-deficient molybdenum oxide nano material provided by the invention, L-/D-Cys-MoO_2.83(blue) has the effect of strong near infrared absorption, has good permeability and is easy to enter tumor cells; by using a corresponding chiral light source for irradiation (808nm), the PTT treatment effect of the PTT can be greatly enhanced and can reach 2-10 times of that of the traditional molybdenum oxide material;

in the chiral oxygen-deficient molybdenum oxide nano material provided by the invention, L-/D-Cys-MoO₂The (brown) has the effect of strong absorption in a visible light region (400-650nm), has good permeability and is easy to enter tumor cells; by using a corresponding chiral light source for irradiation (532nm), the PTT treatment effect can reach 2-10 times of that of the traditional molybdenum oxide material; and L-/D-Cys-MoO_2.68(Green) as an intermediate material between the two materials, although the chiral selective absorbing material can also have a certain effect in PTT, the effect is not obvious enough and only serves as a reference control.

Therefore, the chiral oxygen-deficient molybdenum oxide nano material provided by the invention is very suitable for preparing tumor therapeutic agents. The tumor therapeutic agent can be used as a photothermal material for photothermal therapy, can also enhance the efficiency of photothermal therapy and provide photothermal therapy in the visible light range, provides a path for photothermal therapy and is beneficial to tumor synergistic therapy.

In conclusion, the chiral oxygen-deficient molybdenum oxide nano material provided by the invention has a multifunctional multi-channel property, the proportion of each component is convenient to adjust, and the chiral oxygen-deficient molybdenum oxide nano material can be used as a chiral photo-thermal material for treating tumors and has a good application prospect. The preparation method can prepare the chiral nano composite material by a simple redox method, and has the advantages of simple preparation process, environmental protection and low cost.

Drawings

Fig. 1 is a transmission electron microscope image of the chiral optically controllable oxygen deficient molybdenum oxide nanomaterial prepared in example 1.

FIG. 2A is a circular two-image chromatogram of example 1 representing 6 MoOs_3-xThe nano particles have good chiral effect patterns; FIG. 2B is the absorption spectrum of chiral sample for SPR measurement.

FIG. 3 is a Zeta potential diagram of the chiral photo-controllable oxygen-deficient molybdenum oxide nanomaterial prepared in example 1, wherein A is D-Cys-MoO_2.83The Zeta potential diagram of (B) is D-Cys-MoO_2.68The Zeta potential diagram of (C) is D-Cys-MoO₂Zeta potential diagram of (2).

FIG. 4 is a graph showing the temperature-raising capability and heat-generating efficiency of chiral reduced molybdenum oxide prepared in example 2, wherein A is L-/D-Cys-MoO_2.83The temperature rise and drop curve of (blue) material under the irradiation of levorotatory and dextrorotatory laser of 808nm, B is L-/D-Cys-MoO_2.68The temperature rise and fall curve chart of the (green) material under the irradiation of the left-handed laser and the right-handed laser of 808nm, wherein C is L-/D-Cys-MoO₂Temperature rise and fall curve chart of (brown) material under 532nm left-handed and right-handed laser irradiation.

FIG. 5 shows MoO prepared in examples 3-5_3-xEvaluation graph of cytotoxicity of nanoparticles, wherein A is L-Cys-MoO_2.83The material penetrates cell membrane without destroying cell integrity and subcellular structure, and is collected in cytoplasm by transmission electron microscopy, wherein B is/L-Cys-MoO₂Transmission electron microscope image of material aggregation in HeLa cell, C is CCK-8 experiment test different concentration D-Cys-MoO_2.83Cell viability of nanoparticles after 24 hours incubation with HeLa, D is CCK-8 Experimental test for different concentrations of L-Cys-MoO_2.83Cell viability of nanoparticles after 24 hours incubation with HeLa, E is CCK-8 Experimental test for different concentrations of D-Cys-MoO₂Cell viability of nanoparticles after 24 hours incubation with HeLa, F is CCK-8 Experimental test for different concentrations of L-Cys-MoO₂Cell viability plots of nanoparticles after 24 hours incubation with HeLa.

FIG. 6 is the tumor cell ablation experimental graph of the chiral nano thermal therapeutic agent of the type in example 6 under near infrared (808nm) light, wherein A is the interaction of human cervical cancer cell HeLa and nano particle thermal therapeutic agent D-Cys-MoO_2.83(150. mu.g/mL) for 24 hours, followed by irradiation with LCP (levorotatory polarization), LP (linearly polarized light) and DCP (dextrorotatory polarization) at 808nm (1W/cm)²15min) survival rate analysis chart, B human cervical cancer cell HeLa and nano-particle thermal therapy agent L-Cys-MoO_2.83(150. mu.g/mL) for 24 hours, followed by irradiation with LCP (levorotatory polarization), LP (linearly polarized light) and DCP (dextrorotatory polarization) at 808nm (1W/cm)²15min) survival Rate analysis plot, C is fluorescence microscopy of D-and L-Cys-MoO_2.83Graph of dead and alive fluorescence staining of treated HeLa tumor cells in 808nm LCP, DCP and LP laser in vitro ablation experiments (ruler: 100 μm).

FIG. 7 is the experimental chart of tumor cell ablation with the hand-operated nano thermal therapeutic agent under visible (532nm) light of example 6, in which A is the thermal therapeutic agent D-Cys-MoO in combination with HeLa for human cervical cancer cell₂(50. mu.g/mL) after 24 hours of co-incubation (1W/cm) after 532nm LCP (levorotatory), LP (linearly polarized) and DCP (dextrorotatory) irradiation²15min) survival rate analysis chart, B is human cervical carcinoma cell HeLa and nano-particle thermal therapy agent L-Cys-MoO₂(50. mu.g/mL) for 24 hours, followed by irradiation with 532nm LCP (levorotatory light), LP (linearly polarized light) and DCP (dextrorotatory light) (1W/cm)²15min) survival Rate analysis of images, C fluorescence microscopy of D-/L-Cys-MoO₂Graph of cell death and live fluorescence staining in 532nm LCP, DCP and LP laser in vitro ablation experiments of treated HeLa tumor cells (ruler: 100 μm).

Detailed Description

The present invention will be described in detail below with reference to examples to make the features and advantages of the present invention more apparent. It should be noted that the examples are for understanding the concept of the present invention and the scope of the present invention is not limited to only the examples listed herein.

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Example 1

80 mg of molybdenum disulfide black powder was dissolved in 46.25 ml of deionized water. 3.75ml of 30% hydrogen peroxide solution was added to the solution with constant stirring. Then stirring is continued until the black solution turns yellow, and then the solution is heated to 80 ℃ to slowly remove the excess hydrogen peroxide. The heating was stopped after the solution turned from yellow to colorless, and the total heating time was approximately 1 hour. The product is a molybdenum trioxide mother liquor. Chiral MoO_3-xThe nanoparticles are realized by gradually reducing the molybdenum trioxide mother liquor. Specifically, about 1.5ml of the mother liquor is taken, and about 5mg of cysteine is added to reduce the mother liquor into L-/D-Cys-MoO_2.83(blue); about 20mg of cysteine was added and reduced to L-/D-Cys-MoO_2.68(green); about 60mg cysteine was added and reduced to L-/D-Cys-MoO₂(brown). Thereafter, the absorption spectrum of the chiral sample was determined by TU-1901 two-photon UV-Vis spectrometer and the chemical valence state was determined by Thermo Scientific^TMK-Alpha^TMThe XPS system measurements, circular dichroism spectroscopy (CD) were characterized by JASCO J-1500CD spectrometer measurements the morphology of the sample particles was determined by a Tecnai F30 transmission electron microscope.

Example 2

The heating curves of surface cysteine-modified Cys-MoO3-x nanoparticles (20D/L, 60D/L, 80D/L) were measured by Script Communicator software, which is a scriptable, cross-platform data terminal. MoO3-x nanoparticles were added to a 24-well plate at 500. mu.L/well. Then irradiating with 808nm (D/L) near infrared light to 20D/L and 60D/L, and irradiating with 532nm (D/L) visible light to 80D/L for 15min per hole. Data were received through temperature probes, one end of which was connected to the computer and the other end was inserted into the corresponding MoO3-x solution. The final temperature-raising capacity curve of MoO2 nanoparticles (20D/L, 60D/L, 80D/L) was determined by averaging three replicates.

6L-/D-Cys-MoO species currently available_3-xThe nanoparticles have good light heating and heat generation efficiency, and the chiral property is evaluated by measuring under 808nm near infrared light and 532nm visible light, wherein the laser power density is 1.0W/cm < 2 > in the experimentMoO_3-xThe photothermal properties of (1). The solution temperature was observed in real time using Script Communicator software. FIG. 4 shows six L-/D-Cys-MoO_3-xThe temperature profile at room temperature (25 ℃) was removed from the solution.

For all tested L-/D-Cys-MoO_3-xThe solution, under laser irradiation at 808nm and 532nm over a period of 5 minutes, the temperature test probe showed a rapid temperature increase from 25 ℃ to about 45 ℃. Evidence of MoO_3-xThe visible light energy can be quickly and effectively converted into local high temperature under the irradiation of laser, and meanwhile, the temperature is increased along with the increase of time. This temperature is sufficient to kill cancer cells, exposing to temperatures above 48 ℃ for 4-6 minutes can cause irreversible damage.

Example 3

As the culture time is prolonged and the cells continue to divide, on the one hand the cells come into contact with each other causing the growth rate to slow down or even stop. On the other hand, cell growth is not favored due to nutrient deficiency and metabolite accumulation. The cells were passaged to grow normally. The flask was removed from the incubator, 1ml of PBS wash serum was added, and after washing, 1ml of trypsin was added to digest adherent cells. Then, the cells were placed in an incubator for 7-8 minutes, and the flask was removed and 1ml of medium was added to neutralize the digestion by trypsin. The cells in the flask were transferred to a centrifuge tube and centrifuged at 800rpm for 5 minutes. After centrifugation, the supernatant was discarded, and 1ml of medium was added and blown uniformly (to prevent cell aggregation). Three flasks were then filled with 4ml of medium and 40. mu.l of diabody (penicillin and streptomycin), respectively. 1ml of cell sap was removed and poured evenly into three flasks and placed in a 37 ℃ 5% carbon dioxide incubator (BNA610, Yamato Scientific Co., Ltd, Japan).

Example 4

Approximately 24 hours prior to the experiment, cells were seeded in 96-well plates at an initial 1 × 105 cells/well. Cys-MoO3-x nanoparticles were then mixed with fresh broth and incubated with HeLa cells at 37 ℃ under 5% CO2 for 24 hours. After incubation, the culture medium was removed and the cells were washed twice with 1 × PBS. Cells were harvested with a cell scraper and washed into 1.5mL centrifuge tubes in 1mL 1 XPBS. After centrifugation, the remaining PBS was decanted. Cells were fixed in electron microscope fixative for 1 hour at room temperature, stained, and sectioned on a TEM grid for imaging with transmission electron microscopy (H7650, Hitachi).

Example 5

Evaluation of different L-/D-Cys-MoO Using the Pre-mix CCK-8 kit (Beyotime)_3-xCytotoxicity of nanoparticles (20D/L, 60D/L, 80D/L) on Hela cells. Hela cells were cultured at 1.5X 10⁴Each cell/well was seeded into a 96-well plate and cultured for 24h, then different concentrations of nanoparticles (0. mu.g/mL, 50. mu.g/mL, 100. mu.g/mL, 150. mu.g/mL, 200. mu.g/mL, 250. mu.g/mL) were added and cultured for an additional 24 h. Incubation was then continued for 1 hour by adding 100. mu.L of medium containing 10. mu.L of CCK-8 solution to each well. Relative cell viability was determined by the CCK-8 assay, and plates were read at 450nm using an enzyme calibrator (spectramax M5, Molecular Device, USA). Cell viability was determined by the ratio of OD experiments and OD blanks. The final toxicity concentration of each nanoparticle was determined by averaging three replicates.

FIG. 5 shows MoO prepared in examples 3-5_3-xCytotoxicity evaluation chart of nanoparticles, type of MoO_3-xThe nanoparticles can penetrate cell membranes without destroying cellular integrity and subcellular structure, and have low cytotoxicity. MoO was shown by transmission electron microscopy after 24 hours of co-incubation with HeLa cells from human cervical carcinoma_3-xCan penetrate cell membrane and aggregate in cytoplasm without destroying cell integrity and subcellular structure (A: D-/L-Cys-MoO)_2.83；B：D-/L-Cys-MoO₂) And the scale is 200 nm. C-F) CCK-8 experiments tested the cell viability of MoO3-x nanoparticles at different concentrations after 24 hours incubation with HeLa (C-D: D-/L-Cys-MoO2.83; E-F D-/L-Cys-MoO₂)。

Example 6

To evaluate the effect of photothermal therapy, Hela cells were initially cultured at 1.5X 10⁴Inoculating each cell/well into 96 cell plates, incubating for 24 hr, adding nanoparticles, incubating for 24 hr, irradiating with 808nm (D, L) near infrared light to 20D/L, irradiating with 532nm (D, L) visible light to 80D/L MoO3-x, and incubating for 15min per wellThe power was 1W/cm 2. Following the irradiation experiment, cell viability was assessed following irradiation using the CCK-8 kit as described previously. Meanwhile, cells were stained with LIVE/DEAD cell imaging kit (Thermo Fisher Scientific), and then LIVE and DEAD cells were visually characterized under a confocal laser scanning microscope (Zeiss, LSM 880).

Fig. 6 is the experimental image of tumor cell ablation of the chiral nano hyperthermia agent of the type in example 6 under near infrared (808nm) light. Human cervical cancer cell HeLa and nano-particle thermal therapy agent A) D-Cys-MoO_2.83(150. mu.g/mL) and B) L-Cys-MoO_2.83(150. mu.g/mL) for 24 hours, followed by irradiation with LCP (levorotatory polarization), LP (linearly polarized light) and DCP (dextrorotatory polarization) at 808nm (1W/cm)²15min) survival rate analysis (CCK-8 experiments), three replicates per group. C) Fluorescence microscopy of D-and L-Cys-MoO_2.83And (3) the dead and live cell fluorescent staining condition of the treated HeLa tumor cells in 808nm LCP, DCP and LP laser in-vitro ablation experiments. A scale: 100 μm. As can be seen from the figure, the chiral sample has obvious selectivity for the absorption of circularly polarized light, so that the temperature of the system can show completely different rising trends in a short time, namely the absorption of the levorotatory light by the levorotatory sample is far greater than that of the dextrorotatory light and the linearly polarized light, D-/L-Cys-MoO_2.83The killing rate of the nano heat therapeutic agent to HeLa cells can reach 3.1 and 3.01 times of that of achiral light through the controllable chiral effect.

FIG. 7 is the tumor cell ablation experimental chart of the hand-operated nano thermal therapeutic agent under visible (532nm) light in example 6, human cervical cancer cell HeLa and nano particle thermal therapeutic agent A) D-Cys-MoO₂(50. mu.g/mL) and B) L-Cys-MoO₂(50. mu.g/mL) for 24 hours, followed by irradiation with 532nm LCP (levorotatory light), LP (linearly polarized light) and DCP (dextrorotatory light) (1W/cm)²15min) survival rate analysis (CCK-8 experiments), three replicates per group. C) Fluorescence microscope imaging of D-/L-Cys-MoO₂And (3) cell death and survival fluorescence staining conditions in 532nm LCP, DCP and LP laser in-vitro ablation experiments of the treated HeLa tumor cells. A scale: 100 μm. D-/L-Cys-MoO₂The killing ratio of the controllable chiral effect of the nano thermotherapy agent to the HeLa cells can reach 2.52 and 2.5 times of that of achiral light. This feature will enable the chiral MoO_3-xNanoparticles play a key role in photothermal therapy of HeLa cancer cells. The lethal efficiency of the photo-thermal treatment of the cancer cells can be selectively enhanced by using the chiral circularly polarized laser, and the energy loss is reduced.

Claims

1. The chiral light controllable oxygen-deficient molybdenum oxide nano material is characterized in that the chemical formula is L-/D-Cys-MoO_3-xWherein X represents a difference in the degree of oxygen deficiency;

according to the degree of oxygen deficiency (x value) and the chirality of the reducing agent used, L-/D-Cys-MoO can be divided_2.83(blue), L-/D-Cys-MoO_2.68(Green) and L-/D-Cys-MoO₂(brown) six different nanoparticles.

2. The chiral optically controllable oxygen deficient molybdenum oxide nanomaterial according to claim 1 wherein the reducing agent is chiral cysteine.

3. The chiral optically controllable oxygen deficient molybdenum oxide nanomaterial according to claim 1, wherein the value of X is adjustable by L-/D-Cys-MoO_3-xThe dosage of the nanosheet and the reducing agent chiral cysteine molecule.

4. The chiral photo-controllable oxygen deficient molybdenum oxide nanomaterial according to claim 1, wherein said chiral photo-controllable oxygen deficient molybdenum oxide nanomaterial, most preferably blue color L-/D-Cys-MoO_3-xIs x = 0.17; green L-/D-Cys-MoO_3-xIs x = 0.32; brown L-/D-Cys-MoO_3-xIs x = 1; i.e. L-/D-Cys-MoO_2.83Is blue, L-/D-Cys-MoO_2.68Is green and L-/D-Cys-MoO₂Is brown.

5. The chiral optically controllable oxygen deficient molybdenum oxide nanomaterial according to claim 1, wherein said chiral optically controllable oxygen deficient molybdenum oxide nanomaterial can be prepared by existing techniques, including any size; the most preferred size is blue: 2.7nm, green: 2.9nm, brown: 28.7 nm.

6. A preparation method of a chiral light-controllable oxygen-deficient molybdenum oxide nano material is characterized by comprising the following steps:

7. The preparation method of the chiral optically controllable oxygen-deficient molybdenum oxide nanomaterial according to claim 6, comprising the following steps:

s3: cooling, taking 1.5ml of mother liquor prepared in S2, and adding a certain amount of cysteine to gradually perform reduction reaction: (L-/D-Cys-MoO)_2.83(blue) plus 5 mg; L-/D-Cys-MoO_2.68(green) 20mg and L-/D-Cys-MoO₂Adding 60mg of brown into the mixture, and reducing the mixture for 4 hours at room temperature to obtain the product.

8. The application of the chiral light-controllable oxygen-deficient molybdenum oxide nano material in preparing a tumor photothermal therapeutic agent.

9. Use according to claim 8, wherein the tumor cells are preferably HeLa cells, skin cancer cells.

10. A tumor therapeutic agent comprising the chiral oxygen-deficient molybdenum oxide nanomaterial of any one of claims 1 to 5 and/or other tumor therapeutic active ingredients.