Shape memory nano composite material as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biological medicine, in particular to a shape memory nanocomposite as well as a preparation method and application thereof. The shape memory nano composite material comprises an anisotropic nano capsule and a photo-thermal material located in the anisotropic nano capsule, the anisotropic nano capsule is converted into a spherical nano capsule under illumination, and the material of the anisotropic nano capsule comprises a thermal response shape memory polymer. And the photo-thermal material is a biodegradable photo-thermal material. A biodegradable photo-thermal material is contained inside the anisotropic nanocapsule, and a cancer cell membrane can be adsorbed outside the anisotropic nanocapsule. Due to the anisotropy of the nanocapsule, the blood circulation time can be prolonged, meanwhile, the nanocapsule has the tumor targeting property, and the immune escape ability and the tumor targeting property of the nanocapsule are further improved through bionic modification of a cancer cell membrane. When reaching a tumor part, the near-infrared light can be utilized to realize intelligent shape transformation, so that cancer cell internalization is finally promoted, and the tumor photo-thermal treatment effect is improved.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a shape memory nanocomposite material and a preparation method and application thereof. Background Art

[0002] The rapid development of nanotechnology has brought unprecedented hope for cancer treatment, especially in improving the specificity and effectiveness of drug delivery. Traditional cancer treatments, such as chemotherapy and radiotherapy, often cause serious side effects on normal tissues due to lack of selectivity and have limited therapeutic effects. For this reason, the development of nanocarriers that can be intelligently regulated and targeted for delivery has become a hot topic in current research.

[0003] Shape, as a key design parameter of nanocarriers, directly affects the drug delivery properties of therapeutic drugs. Studies have shown that anisotropic nanoparticles (such as oblong shapes) are superior to spherical nanoparticles in terms of biodistribution and targeted cell interactions. Compared with spherical nanoparticles, they are more resistant to nonspecific cell elimination when administered systemically. Due to the higher surface area to volume ratio, the targeted interaction of anisotropic nanoparticles with cells is also increased. Studies have also shown that non-spherical particles can successfully evade immune clearance, thereby extending circulation time and enhancing therapeutic effects. However, their internalization rate is slower than that of spherical nanoparticles.

[0004] Therefore, the prior art still needs to be improved and developed. Summary of the invention

[0005] In view of the above-mentioned deficiencies in the prior art, the object of the present invention is to provide a shape memory nanocomposite material and a preparation method and application thereof, aiming to solve the problem of slow internalization speed of existing anisotropic nanoparticles.

[0006] Since existing anisotropic nanoparticles have the problem of slow internalization, a nanoparticle is developed that can achieve intelligent shape transformation, using anisotropic nanoparticles to prolong blood circulation time and accumulate in tumors, and finally using external triggers to transform anisotropic nanoparticles at the tumor site into spherical nanoparticles to promote internalization. Furthermore, coating nanoparticles with naturally derived cell membranes can give nanoparticles the characteristics of specific cell types. Among them, using cancer cell membranes to wrap nanoparticles can achieve the replication of the diversity of antigens on the surface of source cells, giving nanoparticles immune escape and homotypic targeting capabilities.

[0007] Based on this, the present invention combines anisotropic nanoparticles with biomimetic cancer cell membrane coatings to produce synergistic effects, and develops a cancer cell membrane-modified thermally responsive shape memory polymer nanocapsule. Specifically, the anisotropic (elongated, such as rod-shaped or elliptical disk-shaped) nanoparticles developed by the present invention can target tumors because they have a longer circulation time than spherical particles and accumulate better in tumors. At the same time, the surface modification of the cancer cell membrane can further enhance its targeting ability and immune escape ability. When it reaches the tumor site, near-infrared light irradiation is used to make the nanocapsule generate heat, prompting the shape to change to a spherical shape, promoting the internalization of cancer cells, and ultimately achieving efficient cancer treatment.

[0008] The technical solution of the present invention is as follows:

[0009] In a first aspect of the present invention, a shape memory nanocomposite material is provided, comprising anisotropic nanocapsules and a photothermal material located inside the anisotropic nanocapsules, wherein the anisotropic nanocapsules are transformed into spherical nanocapsules under light irradiation.

[0010] The material of the anisotropic nanocapsule includes a thermal responsive shape memory polymer, and the photothermal material is a biodegradable photothermal material.

[0011] Optionally, the shape memory nanocomposite material further comprises cancer cell membranes adsorbed on the outer surface of the anisotropic nanocapsule.

[0012] Optionally, the photothermal material is one or more of black phosphorus quantum dots, titanium carbide quantum dots, bismuth selenide quantum dots, and bismuth oxide selenide quantum dots.

[0013] Optionally, the thermally responsive shape memory polymer is one or more of poly (D, L-lactic acid), poly (D, lactide-trimethylene carbonate), polyurethane, and polylactic acid.

[0014] Optionally, in the shape memory nanocomposite material, the mass percentage of the anisotropic nanocapsules is 80% to 90%, the mass percentage of the photothermal material is 4% to 10%, and the mass percentage of the cancer cell membrane is 4% to 10%.

[0015] Optionally, the anisotropic nanocapsule has an oblong shape and a size of 250-350 nm.

[0016] The second aspect of the present invention provides a method for preparing the shape memory nanocomposite material of the present invention, comprising the steps of:

[0017] Providing a thermally responsive shape memory polymer and a photothermal material, wherein the photothermal material is a biodegradable photothermal material;

[0018] The thermal responsive shape memory polymer and the photothermal material are combined by using an oil-in-water emulsion volatilization method to obtain a spherical nanocapsule containing the photothermal material;

[0019] After the spherical nanocapsules containing the photothermal material are formed into films, they are stretched by an automatic film stretching machine to obtain anisotropic nanocapsules containing the photothermal material, that is, the shape memory nanocomposite material.

[0020] Optionally, after obtaining the anisotropic nanocapsules containing the photothermal material, the method further comprises the following steps:

[0021] The cancer cell membrane is adsorbed on the outer surface of the anisotropic nanocapsule to obtain the shape memory nanocomposite material.

[0022] Optionally, the step of combining the thermally responsive shape memory polymer and the photothermal material by using an oil-in-water emulsion volatilization method to obtain a spherical nanocapsule containing the photothermal material comprises:

[0023] mixing a photothermal material, a thermally responsive shape memory polymer and an oil phase solvent to obtain a mixed solution;

[0024] Dispersing the mixed solution by using probe ultrasound, mixing the dispersed solution with a polyvinyl alcohol aqueous solution, and dispersing the solution again by using probe ultrasound to obtain a second dispersed solution;

[0025] The secondary dispersed solution is added into a polyvinyl alcohol aqueous solution and stirred overnight to volatilize the oil phase solvent, and then collected by centrifugation to obtain spherical nanocapsules containing the photothermal material.

[0026] Optionally, after the spherical nanocapsules containing the photothermal material are formed into films, the steps of stretching them using an automatic film stretching machine to obtain anisotropic nanocapsules containing the photothermal material include:

[0027] Dispersing the spherical nanocapsules containing the photothermal material in a mixed solution of polyvinyl alcohol and glycerol, and air-drying to form a film;

[0028] The formed film is stretched 2 to 4 times at a uniform speed using an automatic film stretching machine, and then the stretched film is stirred and dissolved in ice water, and centrifuged at 8000 to 9000 rpm for 5 to 10 minutes to obtain anisotropic nanocapsules containing photothermal materials.

[0029] The third aspect of the present invention provides a use of the shape memory nanocomposite material of the present invention in preparing a drug for treating tumors.

[0030] Beneficial effects: The shape memory nanocomposite material of the present invention includes anisotropic nanocapsules and photothermal materials located inside the anisotropic nanocapsules. The anisotropic nanocapsules are transformed into spherical nanocapsules under light. The material of the anisotropic nanocapsules includes a thermally responsive shape memory polymer, and the photothermal material is a biodegradable photothermal material. The anisotropic nanocapsules contain biodegradable photothermal materials inside, and cancer cell membranes can be adsorbed on the outside. The anisotropy of the nanocapsule itself enables it to prolong blood circulation time, and it also has tumor targeting. The bionic modification of the cancer cell membrane further improves its immune escape ability and tumor targeting. When reaching the tumor site, near-infrared light can be used to achieve intelligent shape transformation, prompting the anisotropic nanocapsules to be transformed into spherical nanocapsules, ultimately promoting the internalization of cancer cells and improving the photothermal treatment effect of tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a transmission electron microscope image of black phosphorus quantum dots.

[0032] Figure 2 SEM image of BPQDs / PDLLA spherical nanocapsules.

[0033] Figure 3 This is the photothermal heating curve of BPQDs / PDLLA spherical nanocapsules.

[0034] Figure 4 SEM image of BPQDs / PDLLA anisotropic nanocapsules.

[0035] Figure 5 Diagram of the photocontrolled shape memory recovery process of BPQDs / PDLLA anisotropic nanocapsules.

[0036] Figure 6 The figure shows the cytotoxicity results of BPQDs / PDLLA anisotropic nanocapsules modified with cancer cell membranes.

[0037] Figure 7 This is the result of cell photothermal therapy of BPQDs / PDLLA anisotropic nanocapsules modified with cancer cell membranes. DETAILED DESCRIPTION

[0038] The present invention provides a shape memory nanocomposite material and a preparation method and application thereof. To make the purpose, technical solution and effect of the present invention clearer and more specific, the present invention is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0039] An embodiment of the present invention provides a shape memory nanocomposite material, which includes anisotropic nanocapsules and a photothermal material located inside the anisotropic nanocapsules, wherein the anisotropic nanocapsules are transformed into spherical nanocapsules under light.

[0040] The material of the anisotropic nanocapsule includes a thermal responsive shape memory polymer, and the photothermal material is a biodegradable photothermal material.

[0041] In an embodiment of the present invention, a photothermal material such as black phosphorus quantum dots is combined with a thermal responsive shape memory polymer to prepare anisotropic nanocapsules containing photothermal materials inside. The anisotropic nanocapsules can prolong blood circulation time and facilitate tumor targeting. The addition of photothermal materials such as black phosphorus quantum dots gives the anisotropic nanocapsules excellent photothermal effects. Since the anisotropic nanocapsules are composed of thermal responsive shape memory polymers, the shape transformation of the nanocapsules can be remotely controlled by near-infrared light, prompting the anisotropic nanocapsules to be transformed into spherical nanocapsules, thereby promoting the internalization of cancer cells and improving the photothermal treatment effect of tumors.

[0042] In one embodiment, the shape memory nanocomposite material further comprises cancer cell membranes adsorbed on the outer surface of the anisotropic nanocapsule.

[0043] The biomimetic modification of cancer cell membranes further improves the immune escape ability and tumor targeting of shape memory nanocomposites. When reaching the tumor site, near-infrared light can be used to achieve intelligent transformation of the shape of the nanocapsules, ultimately promoting the internalization of cancer cells and improving the photothermal therapy effect of tumors.

[0044] In one embodiment, the photothermal material is one or more of black phosphorus quantum dots, titanium carbide quantum dots, bismuth selenide quantum dots, bismuth oxide selenide quantum dots, and the like.

[0045] Preferably, the photothermal material is black phosphorus quantum dots, which can better endow the anisotropic nanocapsules with excellent photothermal effects.

[0046] Furthermore, the size of the black phosphorus quantum dots is controlled within 3 nm.

[0047] In one embodiment, the thermally responsive shape memory polymer is one or more of poly (D, L-lactic acid) (abbreviated as PDLLA), poly (D, lactide-trimethylene carbonate), polyurethane, polylactic acid, etc.

[0048] Preferably, the thermally responsive shape memory polymer is poly (D, L-lactic acid). Poly (D, L-lactic acid) can better achieve near-infrared light remote control of the shape transformation of nanocapsules, and promote the transformation of anisotropic nanocapsules into spherical nanocapsules.

[0049] In one embodiment, the anisotropic nanocapsules have an oblong shape and a size of 250-350 nm.

[0050] In one embodiment, in the shape memory nanocomposite material, the mass percentage of the anisotropic nanocapsules is 80% to 90%, the mass percentage of the photothermal material is 4% to 10%, and the mass percentage of the cancer cell membrane is 4% to 10%.

[0051] The embodiment of the present invention provides a method for preparing the shape memory nanocomposite material, which comprises the steps of:

[0052] Step A, providing a thermally responsive shape memory polymer and a photothermal material, wherein the photothermal material is a biodegradable photothermal material;

[0053] Step B, combining the thermal responsive shape memory polymer and the photothermal material by using an oil-in-water emulsion volatilization method to obtain spherical nanocapsules containing the photothermal material;

[0054] Step C: After the spherical nanocapsules containing the photothermal material are formed into films, they are stretched using an automatic film stretching machine to obtain anisotropic nanocapsules containing the photothermal material, that is, the shape memory nanocomposite material.

[0055] In an embodiment of the present invention, the purpose is to provide a method for preparing a shape memory nanocomposite material. First, a spherical nanocapsule containing a photothermal material is prepared by an oil-in-water emulsion volatilization method. Then, the spherical nanocapsule containing a photothermal material is stretched by an automatic film stretching machine to form an anisotropic nanocapsule. The shape memory nanocomposite material can be obtained. The anisotropy of the nanocapsule itself enables it to prolong blood circulation time and also has tumor targeting. When it reaches the tumor site, the near-infrared light can be used to realize the intelligent transformation of the shape of the nanocapsule, prompting the anisotropic nanocapsule to transform into a spherical nanocapsule, and finally promoting the internalization of cancer cells and improving the photothermal treatment effect of tumors.

[0056] In one embodiment, after step C, the method further comprises:

[0057] Step D: adsorbing cancer cell membranes on the outer surface of the anisotropic nanocapsules to obtain the shape memory nanocomposite material.

[0058] In the embodiment of the present invention, the outer surface of the anisotropic nanocapsule further disperses and adsorbs cancer cell membranes. The synergistic effect of anisotropic shape and bionic cell membrane modification can greatly prolong blood circulation time and improve tumor targeting.

[0059] In one embodiment, the step D specifically comprises:

[0060] Step D1, dissolving the cancer cell membrane in water by ultrasound to obtain a membrane solution;

[0061] Step D2: mixing the anisotropic nanocapsules containing the photothermal material with the membrane solution, subjecting the mixture to ultrasonic treatment and then centrifugation to obtain the shape memory nanocomposite material.

[0062] In step A, the specific details about the thermally responsive shape memory polymer and the photothermal material are as described above and will not be repeated here.

[0063] In one embodiment, the photothermal material is biodegradable black phosphorus quantum dots, and the size of the black phosphorus quantum dots is controlled within 3 nm.

[0064] In one embodiment, the step B specifically comprises:

[0065] Step B1, mixing a photothermal material, a thermally responsive shape memory polymer and an oil phase solvent (such as dichloromethane, etc.) to obtain a mixed solution;

[0066] Step B2, dispersing the mixed solution by using probe ultrasound, mixing the dispersed solution with a polyvinyl alcohol aqueous solution, and dispersing the solution again by using probe ultrasound to obtain a secondary dispersed solution;

[0067] Step B3, adding the secondary dispersed solution into a polyvinyl alcohol aqueous solution and stirring overnight to volatilize the oil phase solvent, and then collecting by centrifugation to obtain spherical nanocapsules containing the photothermal material.

[0068] In an embodiment of the present invention, a photothermal material such as black phosphorus quantum dots and a thermally responsive shape memory polymer are firstly uniformly dispersed by probe ultrasound; secondly, the dispersed solution is added to a polyvinyl alcohol (PVA) aqueous solution, further dispersed by probe ultrasound, and the oil phase solvent is evaporated in the polyvinyl alcohol aqueous solution. Spherical nanocapsules containing the photothermal material are obtained by centrifugation.

[0069] Among them, PVA has the following functions:

[0070] Emulsifier: PVA is a surfactant that can reduce the interfacial tension between the water phase and the oil phase, allowing the oil phase to be stably dispersed in the water phase, thus forming a stable emulsion;

[0071] Stabilizer: PVA can stabilize the emulsion structure during the emulsion volatilization process, prevent the oil droplets from agglomerating or breaking, and ensure that the final product has a uniform microstructure;

[0072] Film former: After the oil phase solvent evaporates, PVA helps to form a stable solid film or particles. This is because PVA itself can form a uniform film during the drying process and provide structural support.

[0073] In one embodiment, in step B2, the mixed solution is uniformly dispersed under probe ultrasound with a power of 65 to 130 W (such as 65 W, 80 W, 100 W, 130 W, etc.) for 2 to 5 minutes (such as 2 minutes, 4 minutes, 5 minutes, etc.), wherein the ultrasound is extended for 2 to 4 seconds (such as 2 seconds, 3 seconds, 4 seconds, etc.) and stopped for 4 to 8 seconds (such as 4 seconds, 6 seconds, 8 seconds, etc.).

[0074] In one embodiment, the step of dispersing again using probe ultrasound specifically includes: dispersing again uniformly under probe ultrasound with a power of 65 to 130 W for 2 to 5 minutes, wherein the dispersion is performed for 2 to 4 seconds and the dispersion is performed for 4 to 8 seconds.

[0075] In one embodiment, the step C specifically comprises:

[0076] Step C1, dispersing the spherical nanocapsules containing the photothermal material in a mixed solution of polyvinyl alcohol (PVA) and glycerol, and air-drying to form a film;

[0077] Step C2, the formed film is stretched at a uniform speed of 2 to 4 times (such as 2 times) using an automatic film stretching machine, and then the stretched film is stirred and dissolved in ice water, and centrifuged at 8000 to 9000 rpm (such as 9000 rpm) for 5 to 10 minutes (such as 10 minutes) to obtain anisotropic nanocapsules containing photothermal materials.

[0078] In an embodiment of the present invention, spherical nanocapsules containing photothermal materials are dispersed again in a mixed solution of high concentration polyvinyl alcohol and glycerol, dried at room temperature to form a film, and stretched using an automatic film stretching machine to obtain anisotropic nanocapsules containing photothermal materials.

[0079] In a specific embodiment, the method for preparing the shape memory nanocomposite material comprises the steps of:

[0080] Provide black phosphorus quantum dots and poly (D,L-lactic acid);

[0081] The black phosphorus quantum dots are combined with the poly(D,L-lactic acid) by using an oil-in-water emulsion volatilization method to obtain spherical nanocapsules containing black phosphorus quantum dots;

[0082] The spherical nanocapsules containing black phosphorus quantum dots are dispersed in a mixed solution of high-concentration polyvinyl alcohol and glycerol, dried to form a film, and stretched using an automatic film stretching machine to obtain anisotropic nanocapsules containing black phosphorus quantum dots;

[0083] The cancer cell membrane is dispersed and adsorbed on the outer surface of the anisotropic nanocapsule to obtain the shape memory nanocomposite material.

[0084] An embodiment of the present invention provides a use of the shape memory nanocomposite material as described above in preparing a drug for treating tumors.

[0085] The present invention is further described in detail below through specific examples.

[0086] Example 1

[0087] 1. Preparation of black phosphorus quantum dots (BPQDs)

[0088] Weigh 30 mg of black phosphorus block, grind it and disperse it in 30 mL of N-methylpyrrolidone to obtain a 1 mg / mL dispersion; ultrasonicate it in a 300W water bath ultrasound for half an hour, and then ultrasonicate it in a 300W probe ultrasound for 18 hours. The entire ultrasonic process is controlled by an ice bath to be completed below 10°C; then centrifuge at 9000 rpm for 20 minutes, take the supernatant, and continue centrifuging at 12000 rpm for 20 minutes to obtain the final black phosphorus quantum dots (BPQDs). The product obtained in Example 1 was characterized, and the results are as follows: Figure 1 shown. Figure 1 This is the transmission electron microscopy image of BPQDs. Figure 1 It can be seen that BPQDs have good monodispersity and uniform size, with an average size of 2.6 nm.

[0089] 2. Preparation of spherical nanocapsules containing black phosphorus quantum dots (the material of the spherical nanocapsules is PDLLA thermal responsive shape memory polymer, and the spherical nanocapsules containing black phosphorus quantum dots are denoted as BPQDs / PDLLA spherical nanocapsules)

[0090] First, take 20 mg of the thermally responsive shape memory polymer poly (D, L-lactic acid) (PDLLA, Tg = 41 ° C), dissolve it in 1 mL of dichloromethane solution by magnetic stirring, and obtain a dispersion with a concentration of 20 mg / mL. Then, take 1 mg of the BPQDs prepared in step 1 above and add it to the above dispersion, and evenly disperse it for 2 minutes under the probe ultrasound with a power of 130W, including supersonication for 2s and stop for 4s. Subsequently, take 500 μL of the above dispersed solution and add it to 10 mL of 0.25wt% polyvinyl alcohol aqueous solution, and use the probe ultrasound to evenly disperse it for 5 minutes again, including supersonication for 2s and stop for 4s. Finally, add the final mixed solution to 20 mL of 0.25wt% polyvinyl alcohol aqueous solution and stir overnight at a stirring speed of 800 rpm to fully volatilize the dichloromethane. Finally, the supernatant was collected by centrifugation at 3000 rpm for 5 minutes, and then the precipitate was collected by centrifugation at 9000 rpm for 8 minutes and washed twice with water to obtain BPQDs / PDLLA spherical nanocapsules. The obtained product was characterized, and the results are shown in Figure 2 shown. Figure 2 is the SEM image of BPQDs / PDLLA nanocapsules. Figure 2 It can be seen that the prepared nanocapsules are relatively uniformly spherical, have good dispersion, and have an average size of 170 nm.

[0091] 3. Photothermal performance of BPQDs / PDLLA spherical nanocapsules

[0092] The BPQDs / PDLLA spherical nanocapsule solution (the solvent is ultrapure water, the concentration of BPQDs is 50 μg / mL) was placed in a transparent quartz cuvette and the emission wavelength was 808 nm and the power was 1.0 W / cm 2 The laser was irradiated for 10 minutes, and the solution temperature was measured every 30 seconds using an infrared thermal imager. Ultrapure water and PDLLA solution (solvent is ultrapure water) were used as control groups to draw the photothermal temperature rise curve. Figure 3 As shown, as time goes by, the temperature of BPQDs / PDLLA spherical nanocapsules gradually increases, while the temperature of ultrapure water and pure PDLLA as controls hardly changes, indicating that the addition of BPQDs greatly enhances the photothermal warming effect of BPQDs / PDLLA spherical nanocapsules.

[0093] 4. Preparation of anisotropic nanocapsules containing black phosphorus quantum dots (denoted as BPQDs / PDLLA anisotropic nanocapsules)

[0094] BPQDs / PDLLA spherical nanocapsules with a black phosphorus quantum dot concentration of 1 mg / mL were uniformly dispersed in 10 mL of a mixed solution consisting of 10 wt% PVA, 2 wt% glycerol and 88 wt% water, introduced into a 5 cm square culture dish, air-dried at room temperature, and the formed film was stretched 2 times at a uniform speed using an automatic film stretching machine, then the stretched film was stirred and dissolved in ice water, and centrifuged at 9000 rpm for 5 minutes to obtain BPQDs / PDLLA anisotropic nanocapsules. Figure 4 As shown, the prepared BPQDs / PDLLA anisotropic nanocapsules have an oblong shape and a size of about 250 to 350 nm.

[0095] 5. Shape memory properties of BPQDs / PDLLA anisotropic nanocapsules.

[0096] 1 mL of BPQDs / PDLLA anisotropic nanocapsule solution (solvent: ultrapure water, BPQDs concentration: 50 μg / mL) was placed in a power density of 1.0 W / cm 2 The shape memory process was captured by SEM electron microscope. Figure 5 As shown, it can be found that the prepared BPQDs / PDLLA anisotropic nanocapsules can gradually return to their original shape under near-infrared light, and have excellent light-controlled shape memory properties.

[0097] 6. Preparation of cancer cell membrane-modified BPQDs / PDLLA anisotropic nanocapsules (i.e., shape memory nanocomposites)

[0098] 1) Extraction of cancer cell membrane

[0099] The membrane of human breast cancer cell MCF7 was extracted using a membrane protein extraction kit using the instructions provided by Bio-Tech Biotech. Briefly, 2×10 7 MCF7 cells were resuspended in 1 mL membrane protein extract and 1 mM phenylmethylsulfonyl fluoride (PMSF) was added. The cells were gently fully suspended and then cultured in an ice bath for 15 min. The MCF7 cell suspension was frozen in liquid nitrogen and then thawed at room temperature three times. The obtained suspension was centrifuged at 700 g for 10 min, and the supernatant was centrifuged at 4 ° C (14000 g, 30 min) to obtain MCF7 cell membranes. Finally, the precipitate was collected and freeze-dried for further use. All cell membrane extraction processes were carried out in an ice bath.

[0100] 2) Preparation of shape memory nanocomposites

[0101] The MCF7 cell membrane was dissolved in ultrapure water and ultrasonically treated for 2 minutes at an ultrasonic intensity of 50W to obtain a membrane solution with a concentration of 1 mg / mL. Then, 1 mL of BPQDs / PDLLA anisotropic nanocapsules with a black phosphorus quantum dot concentration of 1 mg / mL was added to the membrane solution, and the mixture was ultrasonically treated for 2 minutes at an ultrasonic intensity of 50W to obtain a shape memory nanocomposite dispersed in the aqueous phase. Then, the mixture was centrifuged at 4°C (9000rpm, 5min), the nanoparticle part was taken, and then washed twice with ultrapure water to remove the excess cell membrane, and the MCF7 cell membrane-modified BPQDs / PDLLA anisotropic nanocapsules, i.e., shape memory nanocomposites, were obtained.

[0102] 7. Cytotoxicity of shape memory nanocomposites

[0103] MCF7 cells were seeded into 48-well plates at a density of 1 × 10 per well. 5 cells and cultured in a 5% CO2 incubator at 37°C for 24 hours. Subsequently, the original culture medium was replaced with 200 μL of fresh culture medium containing shape memory nanocomposites with different black phosphorus quantum dot concentrations (0, 1.25, 2.5, 5, 10, 20, 50 and 100 μg / mL). After incubation for 24 hours, the culture medium was replaced with a culture medium containing 10% CCK-8 by volume and incubated for another 1 hour to analyze its cytotoxicity. The absorbance at 450 nm was tested using an ELISA reader (FilterMax F5, Molecular Devices, USA) to measure cell viability. The results are shown in Figure 6 The shape memory nanocomposite material still retains more than 90% of cell activity even at a high concentration of 100 μg / mL, proving that the prepared shape memory nanocomposite material has excellent biosafety.

[0104] 8. Cellular photothermal therapy of shape memory nanocomposites.

[0105] MCF7 cells were seeded in 48-well plates overnight at a density of 1 × 10 per well. 5 Four groups were set up, namely the control group, the laser group, the shape memory nanocomposite group (also called the sample group), and the laser plus shape memory nanocomposite group. The 808nm laser power was 1W / cm 2 The irradiation time was 10 min. Afterwards, the cells were co-cultured with calcein (1 μL) and propidium iodide (1 μL) at 37°C in a humidified atmosphere containing 5% CO2 for 20 min. Figure 7As shown, compared with the other three control groups, the experimental results of the group added with laser and shape memory nanocomposite materials showed significant cell death, thus proving that shape memory nanocomposite materials have excellent tumor cell killing effects.

[0106] In summary, the beneficial effects of the present invention are:

[0107] (1) Anisotropic shape memory polymer nanocapsules containing black phosphorus quantum dots prepared by combining black phosphorus quantum dots with thermoresponsive shape memory polymers can prolong blood circulation time and help improve tumor targeting.

[0108] (2) The addition of black phosphorus quantum dots, a photothermal material, endows the nanocapsules with excellent photothermal effects. Combined with thermally responsive shape memory polymers, the shape transformation of nanoparticles can be remotely regulated by near-infrared light.

[0109] (3) Combining shape factors and cell membrane modifications can synergistically enhance the immune escape ability and tumor targeting of nanocapsules, which is very beneficial for in vivo applications.

[0110] It should be understood that the application of the present invention is not limited to the above examples. For ordinary technicians in this field, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A shape memory nanocomposite material, characterized in that: The invention comprises an anisotropic nanocapsule and a photothermal material located inside the anisotropic nanocapsule, wherein the anisotropic nanocapsule is transformed into a spherical nanocapsule under light. The material of the anisotropic nanocapsule includes a thermal responsive shape memory polymer, and the photothermal material is a biodegradable photothermal material.

2. The shape memory nanocomposite material according to claim 1, characterized in that: The shape memory nanocomposite material also includes cancer cell membranes adsorbed on the outer surface of the anisotropic nanocapsule.

3. The shape memory nanocomposite material according to claim 1, characterized in that: The photothermal material is one or more of black phosphorus quantum dots, titanium carbide quantum dots, bismuth selenide quantum dots, and bismuth oxide selenium quantum dots.

4. The shape memory nanocomposite material according to claim 1, characterized in that: The thermally responsive shape memory polymer is one or more of poly (D, L-lactic acid), poly (D, lactide-trimethylene carbonate), polyurethane, and polylactic acid.

5. The shape memory nanocomposite material according to claim 2, characterized in that: In the shape memory nanocomposite material, the mass percentage of the anisotropic nanocapsules is 80% to 90%, the mass percentage of the photothermal material is 4% to 10%, and the mass percentage of the cancer cell membrane is 4% to 10%. The anisotropic nanocapsule has an oblong shape and a size of 250 to 350 nm.

6. A method for preparing the shape memory nanocomposite material according to any one of claims 1 to 5, characterized in that: Includes steps: Providing a thermally responsive shape memory polymer and a photothermal material, wherein the photothermal material is a biodegradable photothermal material; The thermal responsive shape memory polymer and the photothermal material are combined by using an oil-in-water emulsion volatilization method to obtain a spherical nanocapsule containing the photothermal material; After the spherical nanocapsules containing the photothermal material are formed into films, they are stretched by an automatic film stretching machine to obtain anisotropic nanocapsules containing the photothermal material, that is, the shape memory nanocomposite material.

7. The method for preparing the shape memory nanocomposite material according to claim 6, characterized in that: After obtaining the anisotropic nanocapsules containing the photothermal material, the method further comprises the following steps: The cancer cell membrane is adsorbed on the outer surface of the anisotropic nanocapsule to obtain the shape memory nanocomposite material.

8. The method for preparing the shape memory nanocomposite material according to claim 6, characterized in that: The step of combining the thermal responsive shape memory polymer and the photothermal material by using an oil-in-water emulsion volatilization method to obtain a spherical nanocapsule containing the photothermal material comprises: mixing a photothermal material, a thermally responsive shape memory polymer and an oil phase solvent to obtain a mixed solution; Dispersing the mixed solution by using probe ultrasound, mixing the dispersed solution with a polyvinyl alcohol aqueous solution, and dispersing the solution again by using probe ultrasound to obtain a second dispersed solution; The secondary dispersed solution is added into a polyvinyl alcohol aqueous solution and stirred overnight to volatilize the oil phase solvent, and then collected by centrifugation to obtain spherical nanocapsules containing the photothermal material.

9. The method for preparing the shape memory nanocomposite material according to claim 6, characterized in that: After the spherical nanocapsules containing the photothermal material are formed into films, the steps of stretching them using an automatic film stretching machine to obtain anisotropic nanocapsules containing the photothermal material include: Dispersing the spherical nanocapsules containing the photothermal material in a mixed solution of polyvinyl alcohol and glycerol, and air-drying to form a film; The formed film is stretched 2 to 4 times at a uniform speed using an automatic film stretching machine, and then the stretched film is stirred and dissolved in ice water, and centrifuged at 8000 to 9000 rpm for 5 to 10 minutes to obtain anisotropic nanocapsules containing photothermal materials.

10. Use of the shape memory nanocomposite material according to any one of claims 1 to 5 in preparing drugs for treating tumors.

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