Nano-composite for delivering rapamycin based on targeted peptide modified gold nanoparticles as well as preparation method and application of nano-composite

Abstract

The invention discloses a nano compound (RAP (at) KTP (at) AuNPs) for delivering rapamycin based on targeted peptide modified gold nanoparticles as well as a preparation method and application of the nano compound. In the nano compound, the surfaces of the gold nanoparticles are modified by polyethylene glycol to form a PEG layer; the K3 targeting peptide is connected to the surface of the PEG layer through non-covalent coupling; rapamycin is loaded and wrapped in the PEG layer. SH-PEG-SH is added into the AuNPs solution, and a PEG modified AuNPs solution is obtained through a reaction; diluting the K3 targeting peptide with pure water to obtain a diluted solution, adding the diluted solution into the PEG-modified AuNPs solution, and reacting to obtain a KTP-coated AuNPs solution; the preparation method comprises the following steps: dissolving rapamycin powder by using dimethyl sulfoxide, adding the rapamycin powder into a KTP (at) AuNPs solution, and reacting to obtain the nano-composite RAP (at) KTP (at) AuNPs. The nanocomposite provided by the invention can realize efficient and accurate delivery of rapamycin, and improves the effect of treating renal fibrosis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of nanomedicine, and particularly relates to a kind of gold nanoparticles based on targeted peptide modification delivery rapamycin nanocomposite and its preparation method and application. BACKGROUND

[0002] Gold nanoparticles (AuNPs) have been widely concerned in the field of biomedical, especially in drug delivery system, due to their small size, good biocompatibility and surface modification. Rapamycin (RAP) is a small molecule drug with immunosuppressive and anti-tumor activity, which can regulate cell proliferation by inhibiting mammalian target of rapamycin (mTOR) pathway. In recent years, some studies have shown that rapamycin shows good potential in the treatment of renal fibrosis. However, its clinical application is limited by poor water solubility, low bioavailability, and toxic side effects caused by non-targeted nature. SUMMARY

[0003] The technical problem to be solved by the present application is to provide a kind of gold nanoparticles based on targeted peptide modification delivery rapamycin nanocomposite (RAP@KTP@AuNPs) and its preparation method and application, to realize efficient and accurate delivery of rapamycin, and improve the effect of treating renal fibrosis.

[0004] To solve the above technical problems, according to one aspect of the present application, a kind of gold nanoparticles based on targeted peptide modification delivery rapamycin nanocomposite is provided, comprising: Gold nanoparticles, the surface of which is modified by polyethylene glycol to form a PEG layer; K3 targeting peptide, which is connected to the surface of the PEG layer by non-covalent coupling; Rapamycin, which is loaded and wrapped in the PEG layer.

[0005] According to another aspect of the present application, a preparation method of the above-mentioned gold nanoparticles based on targeted peptide modification delivery rapamycin nanocomposite is provided, comprising: Step one, SH-PEG-SH is added to the AuNPs solution, the pH of the solution is adjusted to 7, and the PEG is modified on the Au nanoparticles under the condition of room temperature and dark stirring to obtain a PEG modified AuNPs solution; Step two, dilute K3 targeting peptide with pure water to obtain a dilute solution, add the dilute solution to the PEG modified AuNPs solution obtained in step one, and react at 37℃ to obtain a KTP@AuNPs solution; Step three, rapamycin powder was dissolved by dimethyl sulfoxide and added into KTP@AuNPs solution, and the reaction was stirred at 37℃ to obtain the nanocomposite of rapamycin delivered by gold nanoparticles modified by targeting peptide RAP@KTP@AuNPs.

[0006] As a preferred embodiment, in step one, the preparation method of AuNPs solution is as follows: sodium citrate solution is boiled, and HAuCl4 solution is added under stirring, the color of the solution is observed, and light pink solution is obtained as AuNPs seed; then, the solution temperature is cooled to 90℃, and sodium citrate and HAuCl4 solution are continuously added, and the reaction is carried out under stirring until the color finally changes to wine red to obtain AuNPs solution.

[0007] As a preferred embodiment, in step two, K3 targeting peptide is diluted into a 1mM solution by pure water. As a preferred embodiment, in step two, after the diluted solution is added into the PEG modified AuNPs solution obtained in step one, the final concentration of K3 targeting peptide is 100μM.

[0008] As a preferred embodiment, in step two, the obtained solution is centrifuged at 4℃ and 10000rpm for 10 minutes to remove excess peptides, and the precipitate is resuspended with deionized water.

[0009] As a preferred embodiment, in step three, the final concentration of rapamycin in the reaction solution is 50μM.

[0010] As a preferred embodiment, in step three, the obtained mixture after reaction is centrifuged at 4℃ and 10000rpm for 25 minutes to remove free rapamycin, and the obtained precipitate is resuspended with PBS solution.

[0011] As a preferred embodiment, the amino acid sequence of K3 targeting peptide is (KKEEE)3.

[0012] According to another aspect of the present application, there is provided the use of the above-mentioned nanocomposite of rapamycin delivered by gold nanoparticles modified by targeting peptide in the preparation of a medicament for treating renal fibrosis.

[0013] The present application reduces the interaction of gold nanoparticles (AuNPs) with the immune system by modifying the gold nanoparticles (AuNPs) with polyethylene glycol (PEG), prolongs the circulation time in vivo, and the K3 targeting peptide is a targeting peptide for renal tubular epithelial cells, which is modified on the gold nanoparticles to obtain a KTP@AuNPs complex, and finally loads the drug rapamycin to obtain a RAP@KTP@AuNPs complex. The complex can achieve targeted delivery to renal tubular epithelial cells and improve the drug concentration in the microenvironment of renal fibrosis. The complex has good dispersity, stability and renal targeting. The targeted drug delivery platform prepared by the present application solves the problems of poor targeting and water solubility, low permeability and bioavailability, and obvious side effects of traditional rapamycin, which provides a new strategy for the treatment of renal fibrosis.

[0014] Experiments show that the gold nanoparticles have good biocompatibility, can reduce the clearance of the monocyte-macrophage system after being modified by polyethylene glycol, prolong the circulation time in vivo (the blood concentration half-life is 2-3 times longer than that of traditional rapamycin injection), and at the same time avoid the use of toxic solvents such as polyoxyethylene castor oil and anhydrous ethanol, significantly reduce the side effects such as allergic reaction and neurotoxicity. In vitro cell activity and toxicity experiments show that the nano-drug provided by the present application improves the cell activity of normal cells (such as rat renal tubular epithelial cells NRK-52E) by 2-4 times compared with rapamycin injection, and reduces the toxicity to the cells by 2-3 times. In vivo animal experiments (UUO model) show that under the same treatment dose, the body weight loss rate of mice is much lower than that of the rapamycin alone group, and the tissue organ toxicity is also lower, but the treatment effect is obviously enhanced compared with the rapamycin alone group. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 TEM scanning diagrams of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs, respectively; Figure 2 DLS analysis diagrams of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs, respectively; Figure 2 In the figure, a is the volume distribution ratio of the particle size of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs, and b is the number distribution ratio of the particle size of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs; Figure 3 Zeta potentials of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs, respectively; Figure 4 PDI analysis diagrams of AuNPs, KTP@AuNPs and RAP@KTP@AuNPs, respectively; Figure 5Cell activity of NRK-52E cells co-cultured with AuNPs, KTP@AuNPs, RAP@KTP@AuNPs and RAP for 24 and 48 hours, respectively; Figure 5 In the formula, a represents cell activity of co-cultured cells for 24 hours, and b represents cell activity of co-cultured cells for 48 hours; Figure 6 Cell toxicity of NRK-52E cells co-cultured with AuNPs, KTP@AuNPs, RAP@KTP@AuNPs and RAP for 24 and 48 hours, respectively; Figure 6 In the formula, a represents cell toxicity of co-cultured cells for 24 hours, and b represents cell toxicity of co-cultured cells for 48 hours; Figure 7 Targeting diagram of AuNPs and RAP@KTP@AuNPs to kidneys at UUO 3, 7 and 14 days, respectively; Figure 8 Figures of changes in body weight of mice, volume of fibrotic kidneys and changes in kidney indicators measured at the end of treatment after different treatments, wherein the kidney indicators are the mass of kidneys after treatment: the mass of kidneys of normal mice; Figure 8 In the formula, a represents changes in body weight of mice after different treatments, b represents changes in volume of fibrotic kidneys after different treatments, and c represents changes in kidney indicators after treatment; Figure 9 H&E staining of kidney sections after different treatments; Figure 10 MASSON staining of kidney sections after different treatments; Figure 11 H&E staining of main organs (heart, liver, spleen, lung and kidney) after different treatments. DETAILED DESCRIPTION

[0016] The existing rapamycin has poor water solubility, insufficient targeting, large toxic side effects, and the existing rapamycin nano delivery system has poor stability, low targeting efficiency, insufficient drug loading capacity and other technical defects. Based on this, the overall concept of the present application is to construct a multifunctional drug delivery platform RAP@KTP@AuNPs, taking gold nanoparticles as the carrier, and improving the biocompatibility after PEG modification, non-covalently combining with the targeting peptide K3 to obtain the targeting ability, and finally loading rapamycin to achieve the purpose of treatment.

[0017] Based on this, a typical embodiment of the present application provides a gold nanoparticle delivery rapamycin nanocomposite based on a targeting peptide, which comprises gold nanoparticles, a targeting peptide (KTP) and rapamycin (RAP) Wherein, the surface of gold nanoparticles is modified by thiol-gold coordination with mercapto polyethylene glycol (SH-PEG-SH, Mw=2000) to form a PEG layer, forming a PEG-modified gold nanoparticle complex, denoted as AuNPs.

[0018] The targeting peptide (KTP) is a K3 targeting peptide, which is connected to the surface of the PEG layer by non-covalent coupling, and the amino acid sequence of the K3 targeting peptide is (KKEEE)3, and the complete sequence can be expanded as: KKEEEKKEEEKKEEE.

[0019] Rapamycin (RAP) is loaded and wrapped in the PEG layer.

[0020] The gold nanoparticle core provides a structural platform for the nanocomplex, the PEG layer provides stealth stability and linker function, the K3 targeting peptide and the drug are combined on the nanoparticle by non-covalent binding, and the targeting peptide endows the nanocomplex with active targeting ability, which can specifically bind to mouse renal tubular epithelial cells and guide the active enrichment of the nanocomplex in the fibrosis site of the kidney, thereby achieving specific recognition and drug delivery to diseased cells. In vivo animal experiments have verified that the targeting effect on the kidney tissue is obvious, and the therapeutic effect is significantly improved.

[0021] The currently reported preparation methods of gold nanoparticle-drug complexes mostly use a step-by-step coupling strategy, but there are problems such as complex process, low failure rate, poor uniformity of complex particle size, unstable drug loading, etc. In addition, the existing complexes are prone to aggregation during in vitro storage (manifested as an increase in particle size and a decrease in dispersibility), resulting in fluctuations in therapeutic effect.

[0022] The present embodiment 1 provides a relatively specific preparation method of a nanocomplex (RAP@KTP@AuNPs) of gold nanoparticles delivering rapamycin based on a targeting peptide.

[0023] Step one: seed-mediated growth method for preparing AuNPs solution: 80 mL of 2.2 mM sodium citrate was added to a three-necked round-bottom flask and boiled, and after boiling, magnetic stirring was continued for 15 min. Under stirring, 535 μL of 25 mM HAuCl4 solution was slowly added for further reaction, and the color of the solution was observed to change from light yellow to light pink. The light pink solution obtained was the AuNPs seed. Then, after cooling the solution to 90°C, 535 μL of 60 mM sodium citrate and 535 μL of 25 mM HAuCl4 were added with an interval of 2 min, and the operation was repeated 4 times. Finally, the reaction was continued for 30 min with magnetic stirring until the color finally changed to wine red. The synthesized product was 30 nm AuNPs. The AuNPs solution was stored at 4°C.

[0024] Step two: 800 mg of SH-PEG-SH was added to the solution synthesized in step one, the pH of the solution was adjusted to 7, and the solution was stirred at room temperature in the dark for 4-6 h to allow the PEG to non-covalently attach to the Au nanoparticles. The excess SH-PEG-SH was removed by centrifugation at 15000 rpm for 30 min and the supernatant was discarded. The particles were re-suspended in deionized water and stored at 4°C.

[0025] Step three: the K3 targeting peptide was diluted with pure water to a 1 mM solution, and a portion of the diluted solution was added to the PEG-modified AuNPs solution prepared in step two to give a final concentration of 100 μΜ of peptide, and the reaction was carried out at 37°C overnight. The resulting solution was centrifuged at 10000 rpm at 4°C for 10 min to remove excess peptide, and the precipitate was re-suspended in deionized water to obtain a KTP@AuNPs solution, which was stored in the dark at 4°C.

[0026] Step four: rapamycin (RAP) powder was dissolved in dimethyl sulfoxide (DMSO) and added to the KTP@AuNPs solution obtained in step three to give a final concentration of 50 μΜ of RAP in the reaction solution. The reaction was carried out at 37°C overnight with stirring. The resulting mixture was centrifuged at 10000 rpm at 4°C for 25 min to remove free RAP, and the precipitate was re-suspended in PBS solution and stored at 4°C.

[0027] The nanocomposite (RAP@KTP@AuNPs) obtained in this example has good dispersibility, and its particle size, potential and ultraviolet can indicate the successful synthesis of the nanodrug. The material has good biocompatibility with cells. When used in cell activity and cytotoxicity experiments, the RAP@KTP@AuNPs experimental group showed the best cell activity and the smallest cytotoxicity. When used in animal experiments, the histopathological sections of the main organs (heart, liver, spleen, lung, kidney) of the mice showed normal cell morphology, indicating that RAP@KTP@AuNPs has good biological safety and does not cause significant systemic toxicity.

[0028] Figure 1 The PEG-modified gold nanoparticles obtained by transmission electron microscopy (TEM) observation are spherical in shape, and the morphology does not change significantly after loading K3 and RAP. Figure 2 DLS analysis of AuNPs, KTP@AuNPs, and RAP@KTP@AuNPs shows that the hydrodynamic particle size gradually increases. Figure 3 Zeta potential experiments show that the modified RAP@KTP@AuNPs exhibit a certain electronegativity. Figure 4PDI analysis chart of AuNPs, KTP@AuNPs, RAP@KTP@AuNPs, respectively. The PDI of the three kinds of nanoparticles in pure water is less than 0.3, among which the PDI of RAP@KTP@AuNPs is the lowest and the dispersity is the best. And the PDI of the three kinds of solutions also has no obvious change after one week, showing good dispersity and stability.

[0029] In vitro cell activity and toxicity detection Figure 5 and Figure 6 .

[0030] The CCK8 experiment was used, which is based on the specific reaction of water-soluble tetrazolium salt compound WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid phenyl)-2H-tetrazole monosodium salt) with cell metabolic activity. The succinate dehydrogenase in the mitochondria of living cells (the activity is positively correlated with the cell survival state) can reduce the tetrazole ring of WST-8 to water-soluble orange yellow formazan dye. The absorbance value (OD value) at 450 nm wavelength of the dye is linearly and positively correlated with the concentration of formazan, and the concentration of formazan is directly related to the number of living cells and metabolic activity. The OD values of different concentrations of nanodrugs in the treatment group and the blank control group were detected by an enzyme-labeled instrument, and the formula for calculating the cell survival rate (I%) was as follows: I% = [(As-Ab) / (Ac-Ab)] × 100%; Wherein, As, Ac, Ab represent the absorbance of the experimental hole, the absorbance of the control hole and the absorbance of the blank hole, respectively.

[0031] During the experiment, the logarithmic value of the corresponding concentration of the drug was taken as the abscissa, and the cell survival rate (%) and cell toxicity (%) were taken as the ordinate. The experimental data was expressed as the average value Mean±SD of three independent experiments. Finally, the data obtained by the experiment was plotted by using Origin 2024 software, and the relationship curve between cell activity and cell toxicity and drug dose was obtained.

[0032] Experimental method (1) Cell plating: NRK-52E cells were inoculated in a 96-well plate at a concentration of 5×10³ / well for culture. When the cell density reached 70%, the corresponding drugs were added to the corresponding groups.

[0033] (2) Drug addition: AuNPs, KTP@AuNPs, RAP@KTP@AuNPs and RAP were placed in a 37℃, 5% CO2 cell incubator for 24h and 48h at concentrations of 0.1, 1, 3, 5, 7μM, respectively.

[0034] (3) Test: After 24h and 48h culture, the cells were treated with 10 μL CCK8 (Nanjing Najikeye Bioengineering Co. Ltd, China) for 2h. The absorbance was measured at 450nm by microplate reader.

[0035] The experimental results show that the inhibition of NRK-52E cells by different concentrations of drugs shows a concentration-dependent behavior. The inhibition rate of the drugs does not show obvious time dependence compared with the culture conditions of 24h and 48h. In the NRK-52E cells, nearly 90% high cell survival rate was observed in 24h and 48h with different concentrations of AuNPs, indicating that AuNPs have low cytotoxicity and good biocompatibility. High concentration of RAP has obvious cytotoxicity to NRK-52E cells, and the survival rate is almost 0. Compared with RAP, RAP@KTP@AuNPs have obvious reduction in cytotoxicity at high concentration, showing better biocompatibility.

[0036] In vivo targeting characterization (see Figure 7 ) (1) Animal modeling: The mice were anesthetized with isoflurane, an oblique incision was made at 1cm near the lower edge of the left rib, the left ureter was exposed, two points were ligated with 5-mesh nylon thread to make it obstructed, and then the two ligation points were cut off. Subsequently, the abdominal incision was sutured with the same nylon thread. The animals were put back into the cage for normal feeding after operation.

[0037] (2) Drug administration: The above synthesized AuNPs and RAP@KTP@AuNPs were modified with ICG, and 100 μL was injected into the tail vein after 3, 7 and 14 days of operation, respectively. The mice were sacrificed 4h after injection, and the internal organs (heart, liver, spleen, lung and kidney) were taken out and washed with PBS. After drying, the small animal near-infrared two-zone live imaging system was observed.

[0038] (3) From the imaging image, it can be seen that the fluorescence luminance of the kidney of the RAP@KTP@AuNPs group modified by the targeting peptide is obviously higher, indicating that its targeting is obviously better than that of the unmodified nanoparticles. It shows that the K3 targeting peptide gives the nanoparticles good kidney targeting.

[0039] In vivo therapeutic effect evaluation (see Figures 8-11 ) Animal modeling: The mice were anesthetized with isoflurane, an oblique incision was made at 1cm near the lower edge of the left rib, the left ureter was exposed, two points were ligated with 5-mesh nylon thread to make it obstructed, and then the two ligation points were cut off. Subsequently, the abdominal incision was sutured with the same nylon thread. The sham operation group only exposed the ureter without ligation. The animals were put back into the cage for normal feeding after operation.

[0040] In this experiment, animals were divided into 5 groups. All groups received intraperitoneal injections of 100 μL once daily, starting on the 3rd day after ureteral ligation. The UUO group (ureteral ligation group) and the sham-operated group received PBS; the KTP@AuNPs group (KTP-modified gold nanoparticle group) and the RAP@KTP@AuNPs group (KTP-modified gold nanoparticles loaded with rapamycin group) received KTP@AuNPs solution containing KTP (final concentration 1 μM) and RAP@KTP@AuNPs solution containing rapamycin (final concentration 1 μM), respectively; the RAP group received 1 μM rapamycin. Clear distinctions were made between the intervention conditions for each group to ensure standardized experimental procedures.

[0041] The weight of all mice was measured before each administration. After 14 days, all mice were sacrificed. Both kidneys were removed and weighed. The heart, liver, spleen, lungs, and kidneys were then soaked in 10% neutral formalin, embedded in paraffin, and stained with hematoxylin and eosin (HE) and masson stain.

[0042] like Figure 8 As shown in the weight change curves, we found that the degree of renal edema in mice in the RAP@KTP@AuNPs group was significantly reduced after treatment, demonstrating a better therapeutic effect compared to other groups. Furthermore, throughout the treatment period, the weight of mice in the RAP@KTP@AuNPs group maintained a steady increase, not significantly different from the sham-operated group, while the weight of animals in the RAP group consistently decreased during treatment. This phenomenon indicates that the RAP@KTP@AuNPs nanocomposite has better drug utilization and biocompatibility than RAP.

[0043] To demonstrate that this targeted drug can treat renal fibrosis, we examined changes in the structure and morphology of renal tubules in kidney tissue using HE and MASSON staining. As shown in 9 and 10, compared with the UUO group, RAP@KTP@AuNPs significantly improved the renal tubular structural damage caused by renal fibrosis, and its therapeutic efficacy was also slightly better than RAP alone.

[0044] In addition, such as Figure 11 As shown, HE staining was used to detect whether the synthesized nanomedicine would affect the major organs of mice. Histopathological sections of the major organs (heart, liver, spleen, lung, and kidney) of mice showed normal cell morphology, indicating that RAP@KTP@AuNPs has good biosafety and did not cause obvious systemic toxicity.

[0045] The scope of protection claimed by this invention is not limited to the specific embodiments described above. For those skilled in the art, this invention can have various modifications and alterations. Any modifications, improvements, and equivalent substitutions made within the concept and principles of this invention should be included within the scope of protection of this invention.

Claims

1. A nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles, characterized in that, include: Gold nanoparticles, the surface of which is modified with polyethylene glycol to form a PEG layer; K3 targeting peptide is non-covalently linked to the surface of the PEG layer; Rapamycin, loaded and encapsulated within a PEG layer.

2. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 1, characterized in that, include: Step 1: Add SH-PEG-SH to the AuNPs solution, adjust the pH of the solution to 7, and react under stirring conditions at room temperature in the dark to modify Au nanoparticles with PEG and obtain a PEG-modified AuNPs solution. Step 2: Dilute the K3 targeting peptide with pure water to obtain a diluted solution. Add the diluted solution to the PEG-modified AuNPs solution obtained in Step 1 and react at 37°C to obtain the KTP@AuNPs solution. Step 3: Dissolve rapamycin powder in dimethyl sulfoxide and add it to the KTP@AuNPs solution. Stir the reaction at 37°C to obtain the nanocomposite RAP@KTP@AuNPs based on targeted peptide-modified gold nanoparticles for rapamycin delivery.

3. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 2, characterized in that: In step one, the AuNPs solution is prepared as follows: Boil sodium citrate solution, add HAuCl4 solution while stirring, observe the solution color, and obtain a light pink solution, which is the AuNPs seed; then, cool the solution temperature to 90℃, continue to add sodium citrate and HAuCl4 solution, react under stirring until the color finally turns wine red, and obtain the AuNPs solution.

4. The method for preparing a nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 2 or 3, characterized in that: In step two, the K3 targeting peptide is diluted with pure water to a 1 mM solution.

5. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 4, characterized in that: In step two, after the dilution solution is added to the PEG-modified AuNPs solution obtained in step one, the final concentration of the K3-targeting peptide is 100 μM.

6. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 5, characterized in that: In step two, the solution obtained from the reaction is centrifuged at 4°C and 10,000 rpm for 10 minutes to remove excess peptides and the precipitate is resuspended in deionized water.

7. The method for preparing a nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 2 or 6, characterized in that: In step three, the final concentration of rapamycin in the reaction solution is 50 μM.

8. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 7, characterized in that: In step three, the mixture obtained after the reaction is centrifuged at 4°C and 10,000 rap for 25 min to remove free rapamycin, and the resulting precipitate is resuspended in PBS solution.

9. The method for preparing the nanocomposite for delivering rapamycin based on targeted peptide-modified gold nanoparticles according to claim 2, characterized in that: The amino acid sequence of the K3 targeting peptide is (KKEEE)3.

10. The use of the nanocomposite of rapamycin delivered by gold nanoparticles based on targeted peptide modification as described in claim 1 in the preparation of a medicament for treating renal fibrosis.

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