CN116603074B - A photoresponsive bionic nanoparticle with multiple functions of phototherapy, chemotherapy and multidrug resistance inhibition and a preparation method thereof - Google Patents

Abstract

The invention discloses a photo-responsive bionic nanoparticle with the functions of phototherapy, chemotherapy and multi-drug resistance inhibition, which can greatly improve the anti-tumor effect through the synergistic effect of a photosensitizer, a chemotherapeutic drug and a multi-drug resistance inhibitor. The nanoparticle consists of an inner core and an outer shell, wherein the outer shell is liposome-erythrocyte membrane vesicle loaded with photosensitizer chlorin e6, and the inner core is a double-drug carrier-free nanoparticle formed by self-assembly of chemotherapeutic drug taxol-multidrug resistance inhibitor curcumin. The preparation method of the photoresponse bionic nano-particles is an antisolvent precipitation method combined with a high-pressure homogenization method, and has obvious core-shell structure morphology; the average particle diameter is 139.7+/-1.5 nm, and the polydispersity index is 0.357+/-0.006; has light responsive drug release characteristics; ROS can be effectively generated under the irradiation of laser, and the optical power efficiency is higher; has remarkable anti-tumor effect in vitro and in vivo and has higher clinical application value.

Description

A photoresponsive bionic nanoparticle with multiple functions of phototherapy, chemotherapy and multidrug resistance inhibition and its preparation method

Technical Field

The present invention belongs to the field of medical technology, and specifically relates to a photoresponsive bionic nanoparticle preparation, and in particular to a photoresponsive bionic nanoparticle preparation having the functions of phototherapy, chemotherapy and multidrug resistance inhibition, and a preparation method and application thereof.

Background technique

Breast cancer is the leading cause of morbidity and mortality among women worldwide and has become one of the most difficult problems facing women. For breast cancer patients, chemotherapy is the preferred treatment method. Chemotherapy can kill tumor cells that proliferate indefinitely, but the occurrence and development of tumor multidrug resistance is the main obstacle to the treatment effect of breast cancer patients. At the same time, most chemotherapy drugs have low water solubility and are difficult to accurately target tumor cells. The combination of chemotherapy and other therapies is currently at the forefront of pharmaceutical research. For example, chemotherapy and photodynamic therapy or chemotherapy drugs and tumor multidrug resistance (Multiple drug resistance, MDR) inhibitors are used simultaneously to exert a synergistic effect. Therefore, the development of a nano-delivery system that can not only reverse the multidrug resistance caused by the long-term use of chemotherapy drugs in patients, but also reduce the biosafety issues caused by chemotherapy drugs and improve the therapeutic effect of chemotherapy drugs on tumors is a promising cancer treatment strategy.

Paclitaxel (PTX) is a taxane compound that has been clinically used for breast cancer chemotherapy since the last century. Paclitaxel can affect microtubule polymerization, inhibit cell division, and thus induce apoptosis of tumor cells. Although paclitaxel has considerable therapeutic effects on various types of breast cancer and is a first-line chemotherapy drug for clinical treatment of breast cancer, studies have shown that the responsiveness of paclitaxel alone to breast cancer treatment is only 50%. Within half a year after chemotherapy, about half of the patients develop obvious paclitaxel resistance, which brings unprecedented difficulties to chemotherapy. There are many mechanisms of tumor multidrug resistance (MDR), among which the resistance mechanism of P-glycoprotein (P-gp) is the most common. When paclitaxel and P-gp inhibitors are used in combination, the problem of MDR is solved. A highly effective anti-tumor chemotherapy drug and another substance that can downregulate MDR are delivered to the tumor site at the same time, which enhances the therapeutic effect of chemotherapy drugs.

Chlorin e6 (Ce6) is a chlorophyll-derived photosensitizer that can penetrate deeper into tissues more effectively and has a strong photodynamic efficiency. It has been approved by the FDA for clinical photodynamic therapy. However, due to the limited penetration depth of light, simple PDT cannot completely kill cancer cells and can easily cause further local recurrence of cancer cells. In previous studies, Ce6 was used in combination with chemotherapy as a photosensitizer, showing good synergistic anti-cancer effects. The comprehensive tumor treatment system combining chemotherapy and photodynamic therapy may be the best strategy for breast cancer treatment.

Curcumin (Cur), a plant polyphenol extracted from turmeric rhizomes, can inhibit the occurrence, development and metastasis of almost all types of tumors. In addition, it has been found that the combination of curcumin and anticancer drugs can overcome tumor multidrug resistance (MDR), thereby improving anticancer efficacy and reducing cytotoxicity. Many studies have shown that the synergistic therapeutic effect of paclitaxel and curcumin in the treatment of breast cancer is more effective than the use of either drug alone. Yasmeen et al. showed that curcumin and vitamin D3 can inhibit aldehyde dehydrogenase-1 (ALDH-1) and MDR, enhance the tumor response to paclitaxel, and the cytotoxic effect shows synergy. Yang et al. reported that the co-delivery of paclitaxel (PTX) and Cur inhibited the activity of non-cancer stem cells (non-bCSCs) and cancer stem cells (bCSCs), thereby inhibiting the growth of breast cancer, showing extremely strong anti-tumor ability.

Due to the different physicochemical properties and in vivo behaviors of chemotherapeutic drugs, photosensitizers, and P-glycoprotein (P-gp) inhibitors, it is difficult to ensure the consistency of their accumulation at tumor sites and pharmacokinetic processes in vivo.

Summary of the invention

The main purpose of the present invention is to provide a photoresponsive bionic nanoparticle with multifunctional functions of phototherapy-chemotherapy-multidrug resistance inhibition, which greatly improves its anti-tumor effect through the synergistic effect of photosensitizer-chemotherapeutic drug-multidrug resistance inhibitor.

The technical solution adopted to achieve the purpose of the present invention is:

The present invention provides a photoresponsive bionic nanoparticle with multiple functions of phototherapy, chemotherapy and multidrug resistance inhibition and a preparation method thereof. The nanoparticle consists of an inner core and an outer shell. The outer shell is a liposome-erythrocyte membrane vesicle loaded with photosensitizer dihydrochlorin e6, and the inner core is a dual-drug carrier-free nanoparticle self-assembled from a chemotherapy drug and a multidrug resistance inhibitor.

Furthermore, the nanoparticles have laser-responsive drug release behavior and can simultaneously exert a combined anti-tumor effect of phototherapy-chemotherapy-multidrug resistance inhibition.

Furthermore, the chemotherapeutic drug-multidrug resistance inhibitor is paclitaxel-curcumin, and in the paclitaxel-curcumin dual-drug carrier-free nanoparticles, the molar ratio of paclitaxel to curcumin is 2:1.

Furthermore, the liposome material includes lecithin, cholesterol, and amphiphilic polymer DSPE-PEG _2000. In the liposome-erythrocyte membrane vesicle, the molar ratio of dihydrochlorin e6 to the liposome carrier material lecithin, cholesterol, and amphiphilic polymer DSPE-PEG2000 is 3:60:20:2.8, and the mass ratio of paclitaxel and dihydrochlorin e6 is 1:1.

The present invention also provides a method for preparing the photoresponsive bionic nanoparticles, which is an anti-solvent precipitation method combined with a high-pressure homogenization method, comprising the following specific steps: (1) dispersing paclitaxel and curcumin in 5 mL of DMF in a certain proportion, injecting them into 15 mL of deionized water under ice bath ultrasound conditions, dialyzing them with distilled water for 2 hours under low temperature stirring, and high-pressure homogenization for several times to obtain paclitaxel-curcumin dual-drug carrier-free nanoparticles. (2) accurately weighing a certain amount of dihydrochlorin e6, lecithin, cholesterol and DSPE-PEG ₂₀₀₀ and dissolving them in 5 mL of chloroform, and evaporating them under reduced pressure in an eggplant-shaped bottle to form a film. Add paclitaxel/curcumin carrier-free nanoparticles and mouse erythrocyte membranes, high-pressure homogenization for several times or continuous extrusion by a liposome extruder to obtain photoresponsive bionic nanoparticles.

The present invention also requires the use of the light-responsive bionic nanoparticles in treating tumor diseases.

Compared with the prior art, the characteristics and beneficial effects of the present invention are:

1. The present invention innovatively proposes a photoresponsive bionic nanoparticle with multiple functions of phototherapy, chemotherapy and multidrug resistance inhibition. The particle size is uniform, the preparation method is simple and easy, the stability is good, and the efficient co-delivery of photosensitizers, chemotherapeutic drugs and multidrug resistance inhibitors is achieved, and the nanoparticle has laser-responsive release behavior.

2. The drugs involved in the present invention are typical drugs in phototherapy and chemotherapy. The innovative combination of the two with multidrug resistance inhibitors through nanotechnology not only greatly improves the bioavailability of the three hydrophobic drugs, but also achieves the synergistic anti-tumor effect of phototherapy-chemotherapy-multidrug resistance inhibition, which has potential clinical application value.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram showing the particle size of light-responsive bionic nanoparticles prepared according to Example 1 of the present invention.

FIG. 2 is the observation result of the transmission electron microscopy experiment of the light-responsive bionic nanoparticles conducted according to Example 2 of the present invention.

FIG3 is a release curve diagram of the light-responsive bionic nanoparticles according to Example 3 of the present invention.

FIG. 4 is an experimental result of measuring the ability of light-responsive bionic nanoparticles to produce singlet oxygen in a test tube according to Example 4 of the present invention.

FIG5 is the anti-tumor efficacy experimental result of the light-responsive bionic nanoparticles on 4T1 cell tumor-bearing mice according to Example 6 of the present invention.

Detailed ways

The present invention is further described below in conjunction with the accompanying drawings and specific embodiments. It should be noted that the following description is only for explaining the present invention and does not limit its content.

Example 1

Preparation of photoresponsive biomimetic nanoparticles (B-Lip@PTX/Cur/Ce6): Paclitaxel/curcumin carrier-free nanoparticles (PTX/Cur NCs) were prepared by anti-solvent precipitation method. Specifically:

PTX (1.5 mg) and Cur (0.2 mg) were dispersed in 5 mL of DMF and then added with 15 mL of deionized water after ultrasonic treatment (100 W) in an ice bath. To remove DMF and free drugs, the resulting solution was transferred to a pre-treated dialysis bag (MW = 8000-14000) and dialyzed with distilled water for 2 h under low temperature stirring. PTX/Cur NCs were obtained by homogenization with a PhD D-3L homogenizer for a certain period of time.

The liposome bilayer containing Ce6 was prepared by a modified thin film method, specifically: Ce6, EPC, Chol, and DSPE-PEG ₂₀₀₀ (3:60:20:2.8, mol/mol) were accurately weighed and dissolved in 5 mL of chloroform, then reduced pressure (-0.1 Pa) in an eggplant-shaped bottle and evaporated to form a film.

Then, the above PTX/Cur NCs solution and the erythrocyte membrane pretreated by conventional methods were ultrasonically treated with liposomes to obtain B-Lip@PTX/Cur/Ce6. Finally, B-Lip@PTX/Cur/Ce6 was homogenized with D-3L for a certain period of time or extruded continuously several times with a liposome extruder (400 nm filter membrane).

The particle size of the photoresponsive biomimetic nanoparticles prepared in Example 1 is shown in Figure 1. As can be seen from Figure 1, the average particle size of B-Lip@PTX/Cur/Ce6 is 139.7 ± 1.5 nm, and the polydispersity index is 0.357 ± 0.006, which is considered to be conducive to accumulation in tumor tissues through passive targeting. The average particle size of PTX/Cur NCs is 232.5 ± 4.4 nm, and the distribution is narrow (PDI = 0.185 ± 0.010).

Example 2

The morphology of B-Lip@PTX/Cur/Ce6 was observed by transmission electron microscopy: a drop of PTX/Cur NCs and B-Lip@PTX/Cur/Ce6 was dropped onto a copper grid and evaporated at room temperature. Then, the morphology was observed by transmission electron microscopy at an accelerating voltage after staining with 2% uranyl acetate solution.

The size of PTX/Cur NCs observed in Example 2 is uniform and round. However, B-Lip@PTX/Cur/Ce6 is irregularly round with a distinct "core-shell" structural morphology, indicating that the red blood cell membrane is successfully coated on the surface of PTX/Cur NCs. In addition, due to the dehydration and wrinkling caused by nanoparticles during the preparation of transmission electron microscopy samples, the average hydrodynamic diameter given by dynamic light scattering measurement usually includes the thickness of the hydration layer, so PTX/Cur NCs and B-Lip@PTX/Cur/Ce6 show a particle size slightly smaller than the average hydrodynamic diameter in the transmission electron microscopy image.

Example 3

The in vitro release curve of B-Lip@PTX/Cur/Ce6 was determined by dynamic membrane dialysis: 100 mL PBS (10 mM, pH 7.4) containing 1% (w/v) SDS was used as the release medium to investigate the release behavior of PTX.

The dialysis bag (MWCO=8000-14000) was preheated with water three times and cooled to room temperature. A certain amount of sample was placed in the dialysis bag and sealed at both ends to prevent leakage. The experiment was carried out in a 37 °C water bath constant temperature oscillator (150 rpm) to investigate the effect of laser on drug release. During the release measurement, the B-Lip@PTX/Cur/Ce6 laser group was continuously irradiated with a 660 nm laser (5 mV/cm ² ). Within 72 h, a total of 3 mL of the release solution was taken 12 times within the preset time, and 3 mL of the release medium preheated at 37 °C was added at the same time. The release behavior of PTX/Cur NCs and B-Lip@PTX/Cur/Ce6 in the dark and without laser irradiation was compared under the same conditions. After filtering the samples with a 0.22 µm syringe-driven filter, the PTX content in the release external solution at different time points was determined by HPLC, and the release curves of PTX in different preparations were plotted as cumulative drug release percentage versus time. The experiment was repeated 3 times.

The in vitro release results of B-Lip@PTX/Cur/Ce6 measured in Example 3 are shown in Figure 3. It can be seen from Figure 3 that PTX in PTX/Cur NCs is rapidly released within 12 hours, with a cumulative release amount of nearly 80%, and is almost completely released within 24 hours. Compared with B-Lip@PTX/Cur/Ce6, the release rate of PTX increases after 660 nm laser irradiation. This phenomenon can be explained by the fact that PTX can only be released when the erythrocyte membrane and liposomes are ruptured, which means that the release rate of PTX depends on the degree of rupture of the erythrocyte membrane and liposomes. Since oxidative stress under photodynamic action can enhance the permeability of liposomes, B-Lip@PTX/Cur/Ce6 has light-responsive drug release characteristics. In addition, B-Lip@PTX/Cur/Ce6 + Laser continued to release within 24 hours, reflecting the sustained release characteristics of the drug encapsulated by the erythrocyte membrane and liposomes, which is beneficial to reduce the leakage of drugs when circulating in the body.

Example 4

The ability of B-Lip@PTX/Cur/Ce6 to produce ¹ O ₂ was determined using the singlet oxygen green fluorescent probe Singlet Oxygen Sensor Green (SOSG). Different preparations including B-Lip@PTX/Cur/Ce6, PTX/Cur NCs, and free Ce6 (Free Ce6) were diluted to specific concentrations (the concentration of each preparation group was equivalent to 20 µg/mL PTX and 20 µg/mL Ce6), and phosphate buffered saline (PBS) was used as the control group, and mixed with SOSG, and the final concentration of SOSG was 2 µM. After irradiating each preparation group with laser (660nm, 5 mW/cm2) for different times, the fluorescence intensity of the oxidation product of SOSG, SOSG-EP, was measured in a fluorescence spectrophotometer. Experimental conditions: Ex = 498 nm, Em = 525.8 nm.

Example 4 The production of singlet oxygen in vitro by B-Lip@PTX/Cur/Ce6 under 660 nm laser irradiation was studied using a SOSG probe. Figure 4 shows that the yield of ROS increases with the increase of laser irradiation time, with a certain time correlation. Under laser irradiation, the fluorescence intensity of B-Lip@PTX/Cur/Ce6 and Free Ce6 gradually increased, indicating that the laser induced a large amount of ¹ O ₂ production, while the fluorescence intensity of PBS and PTX/Cur NCs had almost no fluctuation, and almost no ¹ O ₂ was detected. At the same Ce6 concentration and the same irradiation time, the ¹ O ₂ production induced by B-Lip@PTX/Cur/Ce6 ^was significantly higher than _that induced by Free Ce6, indicating that B-Lip@PTX/Cur/Ce6 can effectively produce ROS under laser irradiation and has higher photodynamic efficiency.

Example 5

The cytotoxicity of PTX preparations was determined in vitro using the MTT method. 4T1, MCF-7, and MCF-7/ADR cell suspensions were seeded into 96-well plates at a density of 3×10 ³ cells per well and cultured for 24 hours. The old culture medium was discarded and replaced with fresh culture medium containing a certain concentration of B-Lip@PTX/Cur/Ce6, PTX/Cur NCs, and Free drug. After 4 hours of culture in the dark, the 96-well plates were further cultured in the dark for 24 hours after irradiation with a 660 nm laser for 5 min. After 4 hours, 150 µL of DMSO was added to each well. The absorbance of each well at 570 nm was recorded using a microplate reader, and the cell survival rate was calculated: cell survival rate (%) = (mean OD of drug group/mean OD of blank group) × 100%. The dose-effect curve was drawn with drug concentration as the horizontal axis and survival rate as the vertical axis.

The results of the cytotoxic effect of B-Lip@PTX/Cur/Ce6 measured in Example 5 are shown in Table 1. MCF-7/ADR cells show resistance to PTX. As shown in Table 1, the IC ₅₀ value of Free PTX + _Cur is lower than that of Free PTX, which may be due to the addition of P-gp inhibitor Cur, which has a reversal effect on MDR. In addition, the combination of chemotherapy and PDT can overcome drug resistance and improve the anti-cancer efficacy. Therefore, B-Lip@PTX/Cur/Ce6 is expected to improve anti-cancer activity through the synergistic effect of PDT and chemotherapy. Under 660 nm laser irradiation, B-Lip@PTX/Cur/Ce6 showed the highest cytotoxicity among the three cell lines, showing the significant advantage of PDT in killing cancer cells. Notably, B-Lip@PTX/Cur/Ce6 + L showed superior anticancer activity against MCF-7 and MCF-7/ADR cells, suggesting that combining enhanced chemotherapy with PDT and MDR reversal agents is a superior strategy for anticancer treatment in vitro.

Table 1 Half inhibitory concentration (IC50) of different preparations on MCF-7, MCF-7/ADR, and 4T1 cells (n = 6)

Example 6

The in vivo antitumor activity of different preparations was evaluated using BALB/c female mice (5-6 weeks, 18-22 g). The breast cancer model was constructed by subcutaneous injection of 1×10 ⁶ /mL of logarithmic phase 4T1 cells into the axilla of each mouse. About 4 days later, 36 mice with an average tumor volume of 50-80 mm ³ were selected for the next experiment. The 36 mice were randomly divided into 6 groups (6 mice in each group). 0.9% saline was used as the control group, and the five experimental groups were: 1) Free drug (equivalent to PTX 5.0 mg/kg, Cur 1.1 mg/kg, and Ce6 4 mg/kg) group; 2) Free drug plus laser group; 3) PTX/Cur NCs (equivalent to PTX 5.0 mg/kg, Cur 1.1 mg/kg); 4) B-Lip@PTX/Cur/Ce6 (equivalent to PTX 5.0 mg/kg, Cur1.1 mg/kg, and Ce6 4 mg/kg); 5) B-Lip@PTX/Cur/Ce6 plus laser group. For the laser group, 4 hours after drug administration, the mice were irradiated with laser (660 nm, 5 mW/cm ² , and the optical fiber probe was 3 cm away from the mouse tumor site). The drug was administered by tail vein injection every other day for a total of 5 times. The long and wide diameters of the mouse tumor were measured with a vernier caliper, and the mouse body weight was weighed. The formula for tumor volume is as follows: tumor volume V (mm ³ ) = 0.5×L×W ² , where L and W are the length and width of the tumor, respectively.

Example 6 The anti-tumor effect of B-Lip@PTX/Cur/Ce6 was studied in a 4T1 tumor-bearing mouse model to evaluate the anti-tumor therapeutic effect of multi-drug combination. Figure 5 shows the changes in tumor volume of mice after treatment with different preparations.

It is obvious that the tumor volume of the B-Lip@PTX/Cur/Ce6 treatment group after laser irradiation was significantly lower than that of the non-laser treatment group and other treatment groups. Compared with the saline group, the efficacy of Free drug was relatively low. The tumor was weighed and calculated at the end of the experiment, and its tumor inhibition rate was only about 17.10%. The inhibition rates of Free drug + L, PTX/Cur NCs, and B-Lip@PTX/Cur/Ce6 were 32.11%, 28.68%, and 27.65%, respectively, while the tumor volume of B-Lip@PTX/Cur/Ce6 with laser irradiation was the largest (61.78%). Freedrug + L also had an inhibitory effect on tumor growth, indicating that PDT does have a significant therapeutic effect on tumors. The improved efficacy of B-Lip@PTX/Cur/Ce6 may be due to the coating of the erythrocyte membrane, which helps B-Lip@PTX/Cur/Ce6 escape phagocytosis and last longer in the circulation, enhancing its accumulation in tumors. In addition, the inhibitory effect of Cur on P-gp reduced the chance of PTX being pumped out of the cell, enhancing the combined chemotherapy/phototherapy treatment effect. The enhanced therapeutic effect of B-Lip@PTX/Cur/Ce6 under laser irradiation may be related to its prolonged circulation time in the body, precise release of loaded drugs after being taken up by tumor cells, and high accumulation in tumor cells, thereby improving the bioavailability of PTX, Cur, and Ce6.

Example 7 Study on the interaction between PTX and Cur molecules and cytotoxicity experiments at different ratios: The fluorescence spectra of PTX and Cur were obtained using a fluorescence spectrophotometer. PTX and Cur were dissolved in an appropriate amount of DMSO. The PTX concentration was configured to be 12 µM, and different concentrations of Cur (0, 12, 24, 36, 48, 60, 72, 84 µM) were added, and the fluorescence quenching spectra of PTX were recorded at 303.15 K, 308.15 K and 313.15 K, respectively. Before the measurement, the prepared solution was vortexed and mixed, and then placed in a water bath at the corresponding temperature for 30 min. Ex was set to 409 nm, and the excitation and emission slits were both 2.5 nm. The synergistic antitumor activity of different ratios of PTX and Cur combinations was determined in vitro using the MTT method. The 4T1 cell suspension was inoculated into a 96-well plate at a density of 3×103 cells per well and cultured for 24 hours. The old culture medium was discarded and replaced with fresh culture medium containing a certain concentration of drug, and the 96-well plate was further incubated for 24 hours. After 4 hours, 150 µL of DMSO was added to each well, and the plate was shaken for 5 min to dissolve the formaldehyde crystals. The absorbance of each well at 570 nm was recorded using a microplate reader. Calculate cell viability: cell viability (%) = (mean OD of drug group/mean OD of blank group) × 100%. The half-maximal inhibitory concentration (IC50) value was calculated by Graphpad Prism 5.0 version, and the half-combination index (CI50) value was calculated by CompuSyn 1.0 version.

The results obtained in Example 7 are shown in Tables 2 and 3. From Table 2, the number of binding sites (n) and the binding constant ( _Ka ) of PTX and Cur can be obtained. The n value is about 2.0, indicating that PTX has about two binding sites on Cur. In addition, the _Ka value>10 ⁵ indicates that PTX has a strong binding affinity with Cur. _{The Ka} value increases with increasing temperature, indicating that the binding effect between the two drugs may be endothermic. The optimal combination ratio of PTX and Cur was determined by an in vitro cytotoxicity experiment on 4T1 cells. PTX and Cur treated cells at different molar ratios, and the half-combination index ( _CI50 ) was calculated (Table 3). _CI50≥1 and _CI50 <1 represent the antagonistic effect and synergistic effect of the combined drug, respectively. When the molar ratio of PTX to Cur was 2:1, the half-inhibitory concentration _IC50 value was the lowest, indicating that the inhibitory effect on cell growth was the greatest. Therefore, in further experiments, the optimal molar ratio of PTX:Cur was selected as 2:1.

Table 2 Thermodynamic parameters of PTX and Cur binary system at different temperatures

Table 3 The half inhibitory concentration (IC ₅₀ ) and half combination index (CI ₅₀ ) values of PTX, Cur and PTX/Cur combination at different drug ratios in 4T1 cells (n=6)

The above is only a preferred embodiment of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims (2)

1. The photo-responsive bionic nanoparticle with the functions of phototherapy, chemotherapy and multi-drug resistance inhibition is characterized by comprising an inner core and an outer shell, wherein the outer shell is a liposome-erythrocyte membrane vesicle loaded with a photosensitizer chlorin e6, the inner core is a chemotherapeutic paclitaxel-multi-drug resistance inhibitor curcumin, and the molar ratio is 2:1 self-assembling to form double-drug carrier-free nano particles;

In the liposome-erythrocyte membrane vesicle, a liposome material comprises lecithin, cholesterol and amphiphilic polymer DSPE-PEG ₂₀₀₀, wherein the molar ratio of chlorin e6 to lecithin, cholesterol and amphiphilic polymer DSPE-PEG ₂₀₀₀ is 3:60:20:2.8; the mass ratio of taxol to chlorin e6 is 1:1.

2. The method for preparing the photoresponsive biomimetic nanoparticle according to claim 1, wherein the anti-solvent precipitation method is combined with the high-pressure homogenization method/liposome extrusion method, comprises the following specific steps:

(1) Dispersing chemotherapeutic drugs and multi-drug resistant inhibitors in DMF according to a certain proportion, injecting into deionized water under ice bath ultrasonic condition, dialyzing with distilled water for 2 hours under low temperature stirring, homogenizing under high pressure for several times to obtain double-drug carrier-free nanoparticles;

(2) Accurately weighing a certain amount of chlorin e6 and liposome materials, dissolving in chloroform, and evaporating under reduced pressure in a eggplant-shaped bottle to form a film; adding the double-drug carrier-free nanoparticle and the red cell membrane of the mouse, homogenizing for several times under high pressure or continuously extruding by a liposome extruder to obtain the photoresponsive bionic nanoparticle.