Targeted drug delivery system based on lamp2b / imtp synergism and preparation process
By constructing a combination of Lamp2b-IMTP fusion protein cells and modified materials, the problems of uneven distribution and poor targeting of drug delivery systems were solved, achieving precise enrichment and efficient delivery of drugs in target cells.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-23
- Publication Date
- 2026-05-26
AI Technical Summary
Existing drug delivery systems suffer from uneven drug distribution in the body, toxic side effects on normal tissues, and poor targeting, which affect treatment efficacy and efficiency.
A targeted drug delivery system based on the synergistic effect of Lamp2b/IMTP was adopted. By constructing cells overexpressing the Lamp2b-IMTP fusion protein, the basic localization function of Lamp2b and the targeted anchoring function of IMTP were utilized. Combined with modified silica and modified chitosan, a porous structure and stable binding were formed to achieve precise drug delivery.
This approach achieves specific enrichment of drugs on target cells, reduces non-specific binding to normal cells, expands the loading capacity, prolongs the circulation time of drugs in the body, avoids drug degradation, and improves the precision and efficiency of treatment.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of exosome technology, specifically to a targeted drug delivery system and its preparation process based on the synergistic effect of Lamp2b / IMTP. Background Technology
[0002] In modern medicine, the effectiveness and targeting of drug delivery systems are key factors in improving treatment outcomes and reducing drug side effects. Traditional drug delivery methods often suffer from uneven drug distribution within the body and toxic side effects on normal tissues. For example, many anticancer drugs, while killing tumor cells, also cause serious damage to other normal tissues, leading to significant suffering for patients during treatment and limiting therapeutic efficacy. Existing targeted drug delivery systems suffer from poor process precision, affecting drug targeting, and have low payload capacity, further limiting product efficiency. Based on this, the present invention provides further improvements. Summary of the Invention
[0003] In view of the shortcomings of the prior art, the purpose of this invention is to provide a targeted drug delivery system and preparation process based on the synergistic effect of Lamp2b / IMTP, so as to solve the problems mentioned in the background art.
[0004] The present invention solves the technical problem by adopting the following technical solution: This invention provides a preparation process for a targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP, comprising the following steps: constructing cells overexpressing the Lamp2b-IMTP fusion protein, culturing cells overexpressing the Lamp2b-IMTP fusion protein, thereby obtaining the targeted drug delivery system.
[0005] Preferably, the specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be one of a reverse transcription vector, a lentiviral vector, or an adenovirus vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
[0006] Preferably, the specific method for preparing the cells overexpressing the Lamp2b-IMTP fusion protein is as follows: S1, Preparation of modified silica agent: Preheat silica at 55-60℃ for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:(7-11). Then add 10-15% of the total amount of preheated silica calcium sulfate whiskers and 5-8% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 3-5 times the total amount of the S2 product, then add 15-25% of the total amount of modified silica agent. Sonicate at 350-400W for 1 hour. After sonication, centrifuge at 10000-30000g for 20-40 minutes, then filter.
[0007] Preferably, the pH of the Tris buffer solution is 8.5-9.0; and the pH of the phosphate buffer solution is 8.6-9.0.
[0008] Preferably, the method for preparing the calcium sulfate whiskers is as follows: Calcium sulfate whiskers are immersed in 5-8 times their weight of a 10-15% sodium dodecylbenzenesulfonate solution, followed by the addition of 10-15% silicon carbide and 2-4% sodium carboxymethyl cellulose, and stirred until homogeneous. The mixture is then filtered and dried to obtain calcium sulfate whisker bodies.
[0009] Preferably, the modified chitosan agent is prepared by: Add 10-15% carbon nanotubes and 5-8% silane coupling agent to the chitosan solution, followed by 3-6% nano-silica sol. Stir thoroughly, then filter and dry to obtain the modified chitosan agent.
[0010] Preferably, the chitosan solution has a mass fraction of 3-6%; the silane coupling agent is silane coupling agent KH560.
[0011] Preferably, the chitosan solution has a mass fraction of 4.5%.
[0012] This invention also provides a targeted drug delivery system prepared using a process for a targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP.
[0013] Compared with the prior art, the present invention has the following beneficial effects: This invention relates to a Lamp2b / IMTP synergistic targeted drug delivery system based on this preparation process. The drug can be specifically enriched in target cells (such as tumor cells) to achieve precise drug delivery. The basic localization function of Lamp2b is that Lamp2b is a transmembrane protein naturally present on the surface of exosomes. It is responsible for mediating the "initial recognition" between exosomes and receptor cells, ensuring that the delivery system, with exosomes as the core carrier, can be effectively recognized and bound by cells, avoiding rapid clearance by the body as a "foreign body". IMTP's targeting and anchoring function: IMTP, an integrin-targeting peptide, can specifically bind to integrin receptors that are highly expressed on the surface of target cells, such as αvβ3 and αvβ5 integrins commonly found in tumor cells, which is equivalent to adding "precise navigation" to the delivery system; Synergistic effect: Lamp2b ensures the membrane compatibility of the delivery system and can stably bind to cells, while IMTP locks onto the "target cells". The combination of the two greatly reduces non-specific binding to normal cells, fundamentally solving the problem of "uneven drug distribution" in traditional systems; Calcium sulfate whiskers (modified with sodium dodecylbenzenesulfonate and added with silicon carbide and sodium carboxymethyl cellulose): have a porous surface structure and good adsorption and dispersibility. They can bind drugs through physical adsorption or electrostatic interaction, thereby increasing the loading capacity. Modified chitosan (with added carbon nanotubes, silane coupling agent KH560, and nano-silica sol): After modification, chitosan (a natural polysaccharide with good biocompatibility) has more surface active groups, which can form a stable bond with drugs (such as negatively charged nucleic acid drugs and small molecule drugs with polar groups). At the same time, the tubular structure of carbon nanotubes can further encapsulate the drugs, thus doubly increasing the loading capacity. This effect is achieved through pH regulation of the buffer system and the enhanced stability of the modified material, preventing the drug from "prematurely degrading or becoming inactive" during delivery. The nano-silica sol, silicon carbide and other components in the modified silica agent can form a "protective shell" on the surface of the delivery system, reducing the degradation of drugs by enzymes (such as nucleases and proteases) in the blood, while avoiding carrier aggregation (traditional systems are easily cleared by macrophages due to aggregation), prolonging the circulation time in vivo, and providing sufficient time for the drug to reach the target site. Detailed Implementation
[0014] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to specific examples. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0015] The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP in this embodiment includes the following steps: constructing cells overexpressing the Lamp2b-IMTP fusion protein, culturing cells overexpressing the Lamp2b-IMTP fusion protein, and thus obtaining the targeted drug delivery system.
[0016] The specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be one of a reverse transcription vector, a lentiviral vector, or an adenovirus vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
[0017] The specific method for preparing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: S1, Preparation of modified silica agent: Preheat silica at 55-60℃ for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:(7-11). Then add 10-15% of the total amount of preheated silica calcium sulfate whiskers and 5-8% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 3-5 times the total amount of the S2 product, then add 15-25% of the total amount of modified silica agent. Sonicate at 350-400W for 1 hour. After sonication, centrifuge at 10000-30000g for 20-40 minutes, then filter.
[0018] In this embodiment, the pH value of the Tris buffer solution is 8.5-9.0; the pH value of the phosphate buffer solution is 8.6-9.0.
[0019] The method for preparing calcium sulfate whiskers in this embodiment is as follows: Calcium sulfate whiskers are immersed in 5-8 times their weight of a 10-15% sodium dodecylbenzenesulfonate solution, followed by the addition of 10-15% silicon carbide and 2-4% sodium carboxymethyl cellulose, and stirred until homogeneous. The mixture is then filtered and dried to obtain calcium sulfate whisker bodies.
[0020] The preparation method of the modified chitosan agent in this embodiment is as follows: Add 10-15% carbon nanotubes and 5-8% silane coupling agent to the chitosan solution, followed by 3-6% nano-silica sol. Stir thoroughly, then filter and dry to obtain the modified chitosan agent.
[0021] In this embodiment, the chitosan solution has a mass fraction of 3-6%; the silane coupling agent is silane coupling agent KH560.
[0022] The chitosan solution in this embodiment has a mass fraction of 4.5%.
[0023] The targeted drug delivery system prepared in this embodiment is based on the Lamp2b / IMTP synergistic effect preparation process.
[0024] Example 1. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP in this embodiment includes the following steps: constructing cells overexpressing the Lamp2b-IMTP fusion protein, culturing cells overexpressing the Lamp2b-IMTP fusion protein, and thus obtaining the targeted drug delivery system.
[0025] The specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be a reverse transcription vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
[0026] The specific method for preparing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: S1, Preparation of modified silica agent: Preheat silica at 55°C for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:7. Then add 10% of the total amount of preheated silica calcium sulfate whiskers and 5% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 3 times the total amount of the S2 product, then add 15% of the total amount of the S2 product modified silica agent. Sonicate at 350W for 1 hour. After sonication, centrifuge at 10000g for 20 minutes, then filter.
[0027] In this embodiment, the pH of the Tris buffer solution is 8.5; the pH of the phosphate buffer solution is 8.6.
[0028] The method for preparing calcium sulfate whiskers in this embodiment is as follows: Calcium sulfate whiskers were immersed in 5 times their weight of a 10% sodium dodecylbenzenesulfonate solution, followed by the addition of 10% silicon carbide and 2% sodium carboxymethyl cellulose, and the mixture was stirred until homogeneous. The mixture was then filtered and dried to obtain calcium sulfate whisker bodies.
[0029] The preparation method of the modified chitosan agent in this embodiment is as follows: Add 10% carbon nanotubes and 5% silane coupling agent to the chitosan solution, then add 3% nano-silica sol, stir thoroughly, filter and dry to obtain the modified chitosan agent.
[0030] In this embodiment, the chitosan solution has a mass fraction of 3%; the silane coupling agent is silane coupling agent KH560.
[0031] The targeted drug delivery system prepared in this embodiment is based on the Lamp2b / IMTP synergistic effect preparation process.
[0032] Example 2. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP in this embodiment includes the following steps: constructing cells overexpressing the Lamp2b-IMTP fusion protein, culturing cells overexpressing the Lamp2b-IMTP fusion protein, and thus obtaining the targeted drug delivery system.
[0033] The specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be one of a reverse transcription vector, a lentiviral vector, or an adenovirus vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
[0034] The specific method for preparing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: S1, Preparation of modified silica agent: Preheat silica at 60°C for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:11. Then add 15% of the total amount of preheated silica calcium sulfate whiskers and 8% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 5 times the total amount of the S2 product, then add 25% of the total amount of the S2 product modified silica agent. Sonicate at 400W for 1 hour. After sonication, centrifuge at 30000g for 40 minutes, then filter.
[0035] In this embodiment, the pH of the Tris buffer solution is 9.0; the pH of the phosphate buffer solution is 9.0.
[0036] The method for preparing calcium sulfate whiskers in this embodiment is as follows: Calcium sulfate whiskers were immersed in 8 times their weight of a 15% sodium dodecylbenzenesulfonate solution, followed by the addition of 15% silicon carbide and 4% sodium carboxymethyl cellulose, and the mixture was stirred until homogeneous. The mixture was then filtered and dried to obtain calcium sulfate whisker bodies.
[0037] The preparation method of the modified chitosan agent in this embodiment is as follows: Add 15% carbon nanotubes and 8% silane coupling agent to the chitosan solution, then add 6% nano-silica sol, stir thoroughly, filter and dry to obtain the modified chitosan agent.
[0038] In this embodiment, the chitosan solution has a mass fraction of 6%; the silane coupling agent is silane coupling agent KH560.
[0039] The targeted drug delivery system prepared in this embodiment is based on the Lamp2b / IMTP synergistic effect preparation process.
[0040] Example 3. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP in this embodiment includes the following steps: constructing cells overexpressing the Lamp2b-IMTP fusion protein, culturing cells overexpressing the Lamp2b-IMTP fusion protein, and thus obtaining the targeted drug delivery system.
[0041] The specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be an adenovirus vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
[0042] The specific method for preparing cells overexpressing the Lamp2b-IMTP fusion protein in this embodiment is as follows: S1, Preparation of modified silica agent: Preheat silica at 58°C for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:9. Then add 12% of the total amount of preheated silica calcium sulfate whiskers and 6.5% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 4 times the total amount of S2 product, then add 20% of the total amount of S2 product modified silica agent, sonicate at 375W for 1 hour, centrifuge at 20000g for 30 minutes, filter, and it is ready.
[0043] The pH of the Tris buffer solution in this embodiment is 8.8; the pH of the phosphate buffer solution is 8.8.
[0044] The method for preparing calcium sulfate whiskers in this embodiment is as follows: Calcium sulfate whiskers were immersed in 6.5 times their weight of a 12.5% sodium dodecylbenzenesulfonate solution, followed by the addition of 12.5% silicon carbide and 3% sodium carboxymethyl cellulose, and the mixture was stirred until homogeneous. The mixture was then filtered and dried to obtain calcium sulfate whisker bodies.
[0045] The preparation method of the modified chitosan agent in this embodiment is as follows: 12.5% of carbon nanotubes and 6.5% of silane coupling agent were added to the chitosan solution, followed by 4.5% of nano-silica sol. The mixture was stirred thoroughly, then filtered and dried to obtain the modified chitosan agent.
[0046] In this embodiment, the chitosan solution has a mass fraction of 4.5%; the silane coupling agent is silane coupling agent KH560.
[0047] The targeted drug delivery system prepared in this embodiment is based on the Lamp2b / IMTP synergistic effect preparation process.
[0048] Comparative Example 1. Unlike Example 3, no modified silica agent was added to the cells overexpressing the Lamp2b-IMTP fusion protein.
[0049] Comparative Example 2. Unlike Example 3, calcium sulfate whiskers were not added during the preparation of the modified silica agent.
[0050] Comparative Example 3. Unlike Example 3, calcium sulfate whiskers are used instead of calcium sulfate whiskers.
[0051] Comparative Example 4. Unlike Example 3, no modified chitosan agent was added.
[0052] Comparative Example 5. Unlike Example 3, carbon nanotubes and silane coupling agents were not added in the preparation of the modified chitosan agent.
[0053] The product performance tests for Examples 1-3 and Comparative Examples 1-5 are as follows: Drug loading determination: Experimental Methods: High-performance liquid chromatography (HPLC) was used. A C18 column (250 mm × 4.6 mm) was used, with methanol-water (70:30, v / v) as the mobile phase, a flow rate of 1 mL / min, and a detection wavelength of 480 nm. Doxorubicin (DOX) standard was accurately weighed, and a standard curve was plotted. 1 mg of the test product's nanovesicles was taken, and after rupture, the DOX peak area was measured, and the loading was calculated (loading = mass of DOX in nanovesicles / total mass of nanovesicles × 100%). Targeted experiments: Experimental methods: The nanovesicles of the test product were labeled with the fluorescent dye DiI (final concentration 5 μM) and co-cultured with HepG2 human liver cancer cells (target cells) that highly express IMTP and normal liver cells LO2 (control cells) for 4 h. After trypsin digestion, the intracellular fluorescence positivity rate (i.e., target binding rate) was detected by flow cytometry.
[0054]
[0055] As can be seen from Examples 1-3 and Comparative Examples 1-5, the doxorubicin loading and targeting of the product in Example 3 of this invention are excellent. Furthermore, the performance of the products tends to deteriorate when no modified silica agent is added in the culture of cells overexpressing Lamp2b-IMTP fusion protein, no calcium sulfate whiskers are added in the preparation of the modified silica agent, calcium sulfate whiskers are used instead, no modified chitosan agent is added, and no carbon nanotubes and silane coupling agents are added in the preparation of the modified chitosan agent. Only when the raw materials are obtained using the specific method of this invention do the product performance effects are most significant.
[0056] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.
[0057] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.
Claims
1. A fabrication process for a targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP, characterized in that, Includes the following steps: By constructing and culturing cells that overexpress the Lamp2b-IMTP fusion protein, a targeted drug delivery system can be obtained.
2. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 1, characterized in that, The specific preparation process for constructing cells overexpressing the Lamp2b-IMTP fusion protein is as follows: Design and synthesize the nucleotide sequence encoding the Lamp2b-IMTP fusion protein; insert the nucleotide sequence into a vector to obtain a vector carrying the target gene; the vector can be a plasmid vector or a viral vector, and the viral vector can be one of a reverse transcription vector, a lentiviral vector, or an adenovirus vector; introduce the vector carrying the target gene into mammalian eukaryotic cells containing stem cells, and screen to obtain cells that stably overexpress the Lamp2b-IMTP fusion protein.
3. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 1, characterized in that, The specific method for preparing the cells overexpressing the Lamp2b-IMTP fusion protein is as follows: S1, Preparation of modified silica agent: Preheat silica at 55-60℃ for 1 hour to obtain preheated silica. Add the preheated silica to a phosphate buffer solution at a weight ratio of 4:(7-11). Then add 10-15% of the total amount of preheated silica calcium sulfate whiskers and 5-8% of the total amount of preheated silica modified chitosan agent. Stir thoroughly, then filter and dry to obtain modified silica agent. S2, cells overexpressing Lamp2b-IMTP fusion protein were cultured until 90% confluence, the culture medium was discarded, the cells were washed with buffer, trypsin was added for digestion, the trypsin was neutralized with serum-containing culture medium, the supernatant was discarded by centrifugation, and the cells were washed again; the buffer was Tris buffer. S3: Place the S2 product in Tris buffer at 3-5 times the total amount of the S2 product, then add 15-25% of the total amount of modified silica agent. Sonicate at 350-400W for 1 hour. After sonication, centrifuge at 10000-30000g for 20-40 minutes, then filter.
4. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 3, characterized in that, The pH of the Tris buffer solution is 8.5-9.0; the pH of the phosphate buffer solution is 8.6-9.
0.
5. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 3, characterized in that, The method for preparing the calcium sulfate whiskers is as follows: Calcium sulfate whiskers are immersed in 5-8 times their weight of a 10-15% sodium dodecylbenzenesulfonate solution, followed by the addition of 10-15% silicon carbide and 2-4% sodium carboxymethyl cellulose, and stirred until homogeneous. The mixture is then filtered and dried to obtain calcium sulfate whisker bodies.
6. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 1, characterized in that, The preparation method of the modified chitosan agent is as follows: Add 10-15% carbon nanotubes and 5-8% silane coupling agent to the chitosan solution, followed by 3-6% nano-silica sol. Stir thoroughly, then filter and dry to obtain the modified chitosan agent.
7. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 6, characterized in that, The chitosan solution has a mass fraction of 3-6%; the silane coupling agent is silane coupling agent KH560.
8. The preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP according to claim 6, characterized in that, The chitosan solution has a mass fraction of 4.5%.
9. A targeted drug delivery system prepared by the preparation process of the targeted drug delivery system based on the synergistic effect of Lamp2b / IMTP as described in any one of claims 1-8.