Nano drug-loaded complex with targeted myocardial function as well as preparation method and application of nano drug-loaded complex

Abstract

The invention relates to a nano drug-loaded complex with a targeted myocardial function as well as a preparation method and application of the nano drug-loaded complex. The preparation method comprises the following steps: constructing a novel, safe and efficient nano drug-loaded complex by utilizing a nano material assembly technology, namely preparing phospholipid micelles by taking distearoyl phosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG) as a main raw material, loading fluorescent coumarin 6 (C6), adding ischemia targeting polypeptide CSTSMLKAC (PEP) to be coupled on the outer side of the DSPE-PEG, wrapping an SIRT6 agonist MDL-800 in the DSPE-PEG, and preparing the novel, safe and efficient nano drug-loaded complex. The preparation method comprises the following steps: designing and constructing to obtain a DSPE-PEG-C6-PEP-MDL-800 (DPCP-MDL-800) complex; on the basis, characterization release and in-vivo distribution of the complex and an improvement effect of the complex on myocardial ischemia reperfusion injury of an aged mouse are evaluated. The novel nano drug-loaded complex drug with the ischemic myocardial targeting function provided by the invention is expected to provide a potential solution for myocardial ischemia reperfusion injury of aged mice.

Description

Technical Field

[0001] The present invention relates to the fields of biomedicine technology and nano-delivery, and in particular to a nano-drug-loaded complex targeting myocardial function, and a preparation method and application thereof. Background Art

[0002] Myocardial ischemia-reperfusion (MI / R) injury is a common clinical cardiac pathological phenomenon, particularly in aging individuals, where MI / R injury is particularly severe due to decreased energy metabolism. Existing treatments have failed to effectively address the energy metabolism issues in aging individuals following myocardial ischemia.

[0003] SIRT6, an epigenetic histone deacetylase, is considered to have a potential protective role in various cardiovascular diseases. Activating SIRT6 may be a potential target for the treatment of myocardial ischemia (MI / R) in aging. Existing studies have shown that SIRT6 deficiency can aggravate MI / R injury, but the specific functions and mechanisms of SIRT6 activation in myocardial ischemia in aging have not been fully investigated. Compared with traditional gene editing methods (such as overexpression), strategies for activating SIRT6 are more consistent with physiological regulatory mechanisms, have greater controllability, lower risk of side effects, and are highly operational, making them particularly suitable for clinical application. MDL-800 is the first reported SIRT6-specific small molecule agonist, capable of specifically activating the deacetylase activity of SIRT6, thereby exerting its biological effects. However, as a small molecule drug, MDL-800 has many limitations with traditional administration methods, such as low bioavailability, poor solubility, and insufficient targeting, which greatly limit its effectiveness in clinical treatment. Therefore, overcoming these limitations and designing an efficient drug delivery system has become an urgent issue.

[0004] Distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) is a commonly used lipid-polymer composite with excellent biocompatibility, stability, and functional properties, and is widely used in the construction of nanoparticle drug carriers. Furthermore, the PEP peptide (Cys-Ser-Thr-Ser-Met-Leu-Lys-Ala-Cys, amino acid abbreviation: CSTSMLKAC) is a peptide sequence obtained through phage display technology and has been shown to have excellent targeting properties to ischemic myocardium.

[0005] In summary, it is urgent to develop a new nano-drug carrier complex that targets ischemic myocardium, has good solubility, enhances drug efficacy and reduces side effects, which can be used to specifically activate myocardial SIRT6 and improve ischemia-reperfusion injury in aging myocardium. Therefore, a new solution to the above problems needs to be proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide a nano drug-loaded complex targeting myocardial function and a preparation method and application thereof, so as to solve the technical problems raised in the background technology.

[0007] To achieve the above object, the present invention provides the following technical solution: a method for preparing a DPCP-MDL-800 complex, comprising at least the following steps:

[0008] A myocardial targeting ligand polypeptide is named PEP, and its amino acid sequence is: CSTSMLKAC.

[0009] A myocardially targeted nano drug-carrying composite carrier, comprising:

[0010] A drug carrier, wherein the drug carrier is distearoylphosphatidylethanolamine-polyethylene glycol DSPE-PEG;

[0011] Myocardial targeting ligand, wherein the myocardial targeting ligand is the above-mentioned polypeptide PEP;

[0012] Active ingredient.

[0013] Furthermore, the composite carrier also includes a fluorescent marker, and the fluorescent marker is fluorescent coumarin 6C6.

[0014] Furthermore, the active ingredient is a compound or biological molecule having the function of treating myocardial ischemia-reperfusion injury.

[0015] Furthermore, the active ingredient is the SIRT6 activator MDL-800.

[0016] Furthermore, the MDL-800 is embedded in the liposome core formed by DSPE-PEG through self-assembly, and the PEP polypeptide is modified on the liposome surface by covalent coupling or physical adsorption to form a composite carrier DPCP-MDL-800.

[0017] Any of the following applications of the composite carrier DPCP-MDL-800:

[0018] (1) Reduce myocardial infarction area;

[0019] (2) Improve cardiac energy metabolism;

[0020] (3) Reduce myocardial ischemia-reperfusion injury in the aging heart.

[0021] The preparation method of the composite carrier DPCP-MDL-800 is characterized by comprising the following steps:

[0022] S1. Dissolve the active ingredient MDL-800 in DMSO at a concentration of 100-200 mg / mL;

[0023] S2. Egg yolk lecithin, cholesterol, C6, DSPE-PEG, and DSPE-PEG-CHP were dissolved in chloroform at a mass ratio of (80-120):(15-40):(1-5):(15-40):(15-5), and sonicated.

[0024] S3. Add the S1 solution to the S2 mixture and mix by ultrasonication;

[0025] S4. removing chloroform by rotary evaporation to form a drug carrier film;

[0026] S5. Hydrate the drug film with deionized water and form emulsion-like liposomes by ultrasonic dispersion;

[0027] S6. PEP polypeptide is added to the emulsion-like liposome to form a DPCP-MDL-800 complex that has myocardial targeting and encapsulates MDL-800.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. The present invention adopts DSPE-PEG as a carrier through the design of a nanoscale drug delivery system. DSPE-PEG is a material with good biocompatibility, which ensures the high safety of the complex and can effectively improve the bioavailability and stability of the drug.

[0030] 2. The design of this invention is based on myocardial targeting applications. The PEP polypeptide obtained through phage screening technology has been proven to have good myocardial targeting ability and can effectively deliver drugs to myocardial tissue. The combination of peptide PEP, DSPE-PEG, and C6 material enhances the carrier's targeting of ischemic myocardium;

[0031] 3. The complex of the present invention can accurately deliver drugs to myocardial tissue through targeted delivery, reduce systemic toxic side effects, and significantly improve the therapeutic effect of the drug, that is, improve the efficacy and reduce toxic side effects;

[0032] 4. The DPCP-MDL-800 complex of the present invention can effectively improve the bioavailability of MDL-800, enhance the drug's myocardial targeting, and significantly improve myocardial energy metabolism, thereby alleviating ischemia-reperfusion injury in aging myocardium. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0034] Figure 1 Schematic diagram of the construction of the DPCP-MDL-800 complex of the present invention;

[0035] Figure 2 Characterization and performance analysis diagram of the DPCP-MDL-800 complex of the present invention;

[0036] Figure 3 This is an analysis diagram of the in vitro release and drug loading performance of the DPCP-MDL-800 complex of the present invention;

[0037] Figure 4 This is a schematic diagram of the myocardial targeting effect of the DPCP-MDL-800 complex of the present invention;

[0038] Figure 5 Schematic diagram of the SIRT6 activation effect of the DPCP-MDL-800 complex of the present invention in the MI / R model of aged mice;

[0039] Figure 6 Schematic diagram of the effect of the DPCP-MDL-800 complex of the present invention on improving cardiac energy metabolism in aged mice with MI / R;

[0040] Figure 7 Schematic diagram showing the effect of the DPCP-MDL-800 complex treatment of the present invention on myocardial function in aging mice with MI / R. DETAILED DESCRIPTION

[0041] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0042] Example 1: This example provides a nano-drug carrier composite with myocardial targeting function.

[0043] The composite carrier comprises:

[0044] Distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) was used as a drug carrier;

[0045] Fluorescent coumarin 6 (C6) was used as a fluorescent marker;

[0046] PEP peptide as a myocardial targeting ligand;

[0047] The SIRT6 activator MDL-800 serves as the active ingredient.

[0048] The composite carrier can carry a single active ingredient, or two or more active ingredients simultaneously, wherein the active ingredient is a compound or biomolecule capable of treating myocardial ischemia-reperfusion (MI / R) injury. The active ingredient is not limited to the SIRT6 activator MDL-800, but can also be other compounds or biomolecules capable of treating myocardial ischemia-reperfusion (MI / R) injury.

[0049] The PEP polypeptide is an ischemia-targeting polypeptide designed and synthesized by the applicant, and its sequence is Cys-Ser-Thr-Ser-Met-Leu-Lys-Ala-Cys (amino acid abbreviation: CSTSMLKAC). Common SEQ ID NO. 1.

[0050] The complex is assembled in a manner that MDL-800 is embedded in the liposome core formed by DSPE-PEG through self-assembly, and the PEP polypeptide is modified on the liposome surface through covalent coupling or physical adsorption.

[0051] Among them, the active ingredient MDL-800 is a SIRT6 activator that improves myocardial energy metabolism by enhancing the activity of myocardial SIRT6.

[0052] Example 2: Construction of DPCP-MDL-800 complex

[0053] At least the following steps are included:

[0054] S1. Dissolve MDL-800 in DMSO at a concentration of 100-200 mg / mL.

[0055] S2. Egg yolk lecithin, cholesterol, fluorescent coumarin 6 (C6), DSPE-PEG, and DSPE-PEG-CHP were dissolved in chloroform at a mass ratio of (80-120):(15-40):(1-5):(15-40):(15-25) and sonicated.

[0056] S3. Add the S1 solution to the S2 mixture and mix by ultrasonication;

[0057] S4. removing chloroform by rotary evaporation to form a drug carrier film;

[0058] Heat the rotary evaporator water bath to 70°C, connect the condenser line, and turn on the condenser. Pour the above solution into the eggplant-shaped flask, install the explosion-proof bottle, and install the rotary evaporator. Close the vent valve and begin vacuuming. Set the initial speed to around 20 rpm and raise the water bath until the water level submerges the liquid in the eggplant-shaped flask. Continue until the chloroform is completely evaporated and a thin film forms on the flask wall.

[0059] S5. Hydrate the drug film with deionized water and form emulsion-like liposomes by ultrasonic dispersion;

[0060] Turn off the condensate, turn off the vacuum pump (set the speed to 0, release the air, and turn off the vacuum), turn off the heat, lower the water bath, and remove the eggplant-shaped bottle. Rehydrate by adding 5 mL of deionized water and vacuum evaporating at 60°C, 17 rpm. Rehydrate for 30 minutes. After 30 minutes, remove the bottle, ultrasonically disperse it, transfer it to a 10 mL glass bottle, and add 5 mL of deionized water.

[0061] S6. PEP polypeptide is added to the emulsion-like liposome to form a complex with myocardial targeting and encapsulating MDL-800.

[0062] Ultrasonic disruption was performed at a power of 20-30%, with a 2-second ultrasonic pause and a 3-second ultrasonic break, for 5 minutes. After the ultrasonication, a short interval of 2 minutes was taken to allow the instrument to cool down, and the above steps were repeated 3 times to form emulsion-like liposomes.

[0063] Example 3: Characterization of DPCP-MDL-800 complex

[0064] See Figure 1 , a nano drug-loaded complex with ischemic myocardial targeting function, DPCP-MDL-800 complex was prepared by the method described in Example 1, see Figure 2-Figure 3 In order to verify the characterization of the nano-drug-loaded composite with ischemic myocardial targeting function, the following method was used:

[0065] The morphology of the complex was observed by TEM, and the complex was irregular spherical;

[0066] Use a copper mesh support membrane (its material must be compatible with the liposome components) and add the liposome nanoparticle solution onto the support membrane to ensure that the droplets are evenly distributed. Be careful to avoid contamination by dust and impurities, and control the liposome nanoparticle solution to avoid excessive concentration that causes it to aggregate. Let the sample dry naturally. Load the prepared sample onto the TEM sample holder as quickly as possible (to avoid structural changes caused by prolonged sample exposure), ensure that the sample is positioned accurately, and avoid contamination. Use the TEM's focusing system and contrast adjustment to ensure that the sample details are clearly visible. Adjust the exposure time and contrast to take high-resolution images of the sample. Analyze the collected images to observe the morphology, size, and distribution of the liposome nanoparticles.

[0067] DLS and Zeta potential were used to test the particle size and surface charge of the complex to ensure that it had uniform particle size and negative charge characteristics;

[0068] The liposome sample was dispersed with pure water (selecting a suitable dispersion medium will affect the particle size and zeta potential of the liposome) and diluted to 10 -6w / v, ensure that there are enough particles for tracking. Use an NTA instrument equipped with a high-performance camera and laser system, set the appropriate electrophoresis voltage to ensure that the liposome particles move stably in the electric field. Control the test temperature to 25±0.1℃ (to ensure the accuracy of the measurement results), inject the sample into the PS particle size cell, and use dynamic light scattering for particle size testing. Inject the sample into the capillary electrode, start tracking the liposome particles in the NTA instrument, and perform the ZETA potential test at the same time (usually the same laser and electrophoresis conditions as the particle size analysis). Each sample is tested at least 3 times (the repeatability of the test results and their standard deviation), record the position and velocity of the particles, collect enough data points to obtain an accurate particle size distribution curve; collect ZETA potential data, and calculate the average ZETA potential. Use NTA software to post-process the collected data to obtain quantitative results of particle size distribution and ZETA potential, and analyze and evaluate the stability and dispersibility of the liposomes.

[0069] The fluorescence characteristics of the complex were analyzed by fluorescence spectroscopy, which showed a maximum fluorescence intensity at 502 nm, consistent with the fluorescence characteristics of C6;

[0070] The use of fluorescent molecule C6 as a tracer molecule makes the in vivo distribution of the complex and the drug release process more transparent, making it easier to track and evaluate the targeting and release effects of the drug.

[0071] The concentration of MDL-800 in the complex was approximately 1274.55 μg / mL, indicating that the complex was well loaded with drug.

[0072] Figure 2 A: TEM image of the DPCP-MDL-800 complex, which shows the morphology of the DPCP-MDL-800 complex, indicating that the complex has an irregular spherical structure.

[0073] Figure 2 B: Fluorescence spectrum analysis results of the complex. This figure shows the fluorescence spectrum of the DPCP-MDL-800 complex, indicating that the complex has a maximum fluorescence intensity at 502 nm, which is consistent with the fluorescence characteristics of C6.

[0074] Figure 2 CD: DLS and Zeta potential analysis results of the complex. This figure shows the particle size distribution and Zeta potential of the complex, indicating that the complex has uniform particle size and negative charge.

[0075] Figure 3 A: In vitro release results of the complex. This figure shows the in vitro release curve of the complex, indicating that the complex has good release ability in vitro and the sustained release time exceeds 80 hours.

[0076] Figure 3B: Drug loading results of the complex. This figure shows the drug loading of the complex. The MDL-800 content in the complex is approximately 1274.55 μg / mL.

[0077] Overall, the complex appeared to be an irregular spherical shape under transmission electron microscopy observation, with a maximum fluorescence intensity at 502 nm, consistent with the characteristics of the fluorescent molecule C6. Dynamic light scattering test showed that the particle size of the complex was 100-500 nm, and Zeta potential test showed that the surface charge was negative. The complex was well released in vitro, lasting for more than 80 hours. The MDL-800 content in the complex was approximately 1274.55 μg / mL. The complex was delivered to the ischemic myocardium in the target area by loading the MDL-800 small molecule agonist, and the complex had an ischemic myocardial enrichment effect at 6 hours of ischemia-reperfusion.

[0078] Example 4: Application of DPCP-MDL-800 complex in the treatment of myocardial ischemia-reperfusion

[0079] This embodiment is an application description of the nano-drug complex with ischemic myocardial targeting function based on the above-mentioned embodiment 2:

[0080] See Figure 4 , a nano drug-loaded complex with ischemic myocardial targeting function is used in the preparation of preventive or therapeutic drugs, and the complex is delivered to the ischemic myocardium in the target area by loading the MDL-800 small molecule agonist.

[0081] Adult mice were treated with the complex (10 mg / kg) via tail vein for 6 hours before MI / R surgery. Figure 4 A), in vitro tissue fluorescence imaging was used to observe its distribution at 3h, 6h, 24h, and 48h after reperfusion. The results showed that the complex was enriched in the ischemic myocardium at 6h after reperfusion ( Figure 4 B), compared with the Sham group, confirmed its ischemia targeting effect ( Figure 4 C). Immunofluorescence of tissue sections at different time points also demonstrated that the complex was enriched in the ischemic myocardium at 6 h of reperfusion ( Figure 4 D).

[0082] Example 5: Application of DPCP-MDL-800 complex in targeting myocardial SIR6 molecule

[0083] This embodiment is an application description of the nano-drug complex with ischemic myocardial targeting function based on the above-mentioned embodiment 2:

[0084] See Figure 5 , the nano-drug carrier complex with ischemic myocardial targeting function is used in the preparation of myocardial-specific SIRT6 agonist non-diagnostic treatment methods.

[0085] In vitro release of the complex: 200 μL of the complex solution (containing the DPCP-MDL-800 complex) was placed in a dialysis bag, placed in a PBS solution, and released at 37°C. The results showed that the DPCP-MDL-800 complex had good in vitro release ability, with a sustained release time of more than 80 hours.

[0086] Regular sampling and measurement of release were performed using inductively coupled plasma mass spectrometry (ICP-MS) using an Agilent 7800 with settings of 20 rpm pump speed, 1.00 L / min nebulizer flow, 1.00 L / min auxiliary gas, 40 s sample flushing time, and 1550 W radio frequency power.

[0087] The complex was administered via tail vein injection to aged mice to study its therapeutic efficacy after MI / R surgery. SIRT6 activity was analyzed by Western blot to assess the efficacy of the complex.

[0088] The MI / R model was established in vivo after 6 hours of tail vein administration of the complex DPCP-MDL-800 (10 mg / kg) to naturally aged mice. Figure 5 A). Western Blot analysis of histone acetylation levels 24 hours after reperfusion showed a significant decrease in H3K9ac and H3K56ac, indicating SIRT6 activation, demonstrating the release and activation of MDL-800 within the complex ( Figure 5 B).

[0089] Example 6: DPCP-MDL-800 complex in preventing or improving energy metabolism in aging ischemic myocardium

[0090] This embodiment is an application description of the nano-drug complex with ischemic myocardial targeting function based on the above-mentioned embodiment 2:

[0091] See Figure 6 , the nano drug-carrying complex with ischemic myocardial targeting function is used to prepare drugs for preventing or improving the energy metabolism of aging ischemic myocardium.

[0092] Kit to detect myocardial PDHc activity ( Figure 6 A) Lactic acid content ( Figure 6 B) ATP synthase activity ( Figure 6 C) and ATP content ( Figure 6 D) Results showed that PDHc activity, ATP synthase activity, and ATP content were significantly decreased in ischemic myocardium, while lactate content was increased. This condition was ameliorated by pre-administration of the DPCP-MDL800 complex. This demonstrates that targeted activation of SIRT6 in ischemic myocardium can improve PDHc activity and restore mitochondrial energy metabolism.

[0093] Example 7: Application of DPCP-MDL-800 complex in preventing or treating MI / R in aging

[0094] This embodiment is an application description of the nano-drug complex with ischemic myocardial targeting function based on the above-mentioned embodiment 2:

[0095] See Figure 7 , the application of nano-drug-loaded complexes with ischemic myocardial targeting function in the preparation of drugs for preventing or treating aging MI / R.

[0096] The myocardial infarction area was evaluated by TTC / Evans Blue double staining and it was found that the myocardial infarction area in the DPCP-MDL800 complex-treated group was smaller than that in the control group ( Figure 7 A); serum LDH levels also reflected the reduction of myocardial damage in mice ( Figure 7 Echocardiography assessment of cardiac function revealed that DPCP-MDL800 complex pretreatment significantly improved left ventricular systolic function during MI / R ( Figure 7 C); TUNEL detection of myocardial cell death showed that the complex group alleviated ( Figure 7 D) The above results indicate that myocardial-specific targeted delivery of DPCP-MDL800 complex effectively alleviates ischemic vulnerability of aging myocardium in a whole animal model.

[0097] In summary:

[0098] This invention, for the first time, organically integrates the ischemic myocardial targeting functions of DSPE-PEG phospholipid micelles, the MDL-800 small molecule drug, and the PEP peptide into a multifunctional complex. This complex creates a highly efficient cardiovascular-targeted delivery system. By constructing a DSPE-PEG-based nanoparticle drug delivery system, combining the MDL-800 small molecule drug with the PEP peptide, it successfully achieves myocardial-specific targeted delivery and demonstrates significant therapeutic efficacy in the ischemic vulnerability of aging myocardium. This novel nanoparticle drug system provides an effective drug delivery platform for the treatment of ischemic-reperfusion injury in aging myocardium and holds significant clinical promise.

[0099] Compared to direct delivery of traditional small molecule drugs, this targeted sustained-release drug (DPCP-MDL-800) significantly enhances the drug's myocardial specificity and bioavailability, while effectively reducing systemic toxic side effects. This invention effectively improves the bioavailability of MDL-800, enhances its myocardial targeting, and specifically activates myocardial SIRT6 at low doses, significantly improving cardiac energy metabolism and alleviating ischemia-reperfusion injury in aging myocardium. This approach holds significant clinical application value.

[0100] 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 embodied 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 illustrative and non-restrictive, and the scope of the invention is defined by the appended claims, not the foregoing description, and all variations within the meaning and range of equivalents of the claims are intended to be included therein. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

Claims

1. A myocardial targeting ligand polypeptide, characterized in that: The polypeptide is named PEP, and its amino acid sequence is: CSTSMLKAC.

2. A nano drug-carrying composite carrier targeting the myocardium, characterized in that: The composite carrier comprises: A drug carrier, wherein the drug carrier is distearoylphosphatidylethanolamine-polyethylene glycol DSPE-PEG; A myocardial targeting ligand, wherein the myocardial targeting ligand is the polypeptide PEP according to claim 1; Active ingredient.

3. The composite carrier according to claim 2, characterized in that The composite carrier also includes a fluorescent marker, which is fluorescent coumarin 6C6.

4. The composite carrier according to claim 2, characterized in that The active ingredient is a compound or biological molecule having the function of treating myocardial ischemia-reperfusion injury.

5. The composite carrier according to claim 3, characterized in that: The active ingredient is the SIRT6 activator MDL-800.

6. The composite carrier according to claim 5, characterized in that: The MDL-800 is embedded in the liposome core formed by DSPE-PEG through self-assembly, and the PEP polypeptide is modified on the liposome surface through covalent coupling or physical adsorption to form a composite carrier DPCP-MDL-800.

7. Any of the following uses of the composite carrier DPCP-MDL-800 according to claim 5: (1) Reduce myocardial infarction area; (2) Improve cardiac energy metabolism; (3) Reduce myocardial ischemia-reperfusion injury in the aging heart.

8. The method for preparing the composite carrier DPCP-MDL-800 according to claim 5, characterized in that The following steps are involved: S1. Dissolve the active ingredient MDL-800 in DMSO at a concentration of 100-200 mg / mL; S2. Egg yolk lecithin, cholesterol, C6, DSPE-PEG, and DSPE-PEG-CHP were dissolved in chloroform at a mass ratio of (80-120):(15-40):(1-5):(15-40):(15-5), and sonicated. S3. Add the S1 solution to the S2 mixture and mix by ultrasonication; S4. removing chloroform by rotary evaporation to form a drug carrier film; S5. Hydrate the drug film with deionized water and form emulsion-like liposomes by ultrasonic dispersion; S6. PEP polypeptide is added to the emulsion-like liposome to form a DPCP-MDL-800 complex that has myocardial targeting and encapsulates MDL-800.

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