CN-121975095-A - Polymer, targeting nano system and application thereof

Abstract

The application relates to a polymer, a targeting nano system and application thereof. The targeting nano system comprises an assembly body, wherein the surface of the assembly body comprises a bi-5-hydroxytryptamine ligand which is covalently coupled with the assembly body, the assembly body takes a hydrophobic organic polymer molecule and a thermally responsive gas prodrug as a hydrophobic core, an amphiphilic biomedical high polymer material with good biocompatibility as a carrier, and the hydrophobic organic polymer molecule is the polymer. In addition, the application also relates to the application of the targeting nano system in preparing the multifunctional thrombolytic nano preparation. The application realizes the strong, fixed-point and safe thrombolysis effect, and effectively prevents the formation of the re-thrombosis.

Inventors

• SONG HANG
• SONG JIANWEN

Assignees

• 中国医学科学院北京协和医院

Dates

Publication Date

20260505

Application Date

20260205

Claims (10)

1. 1. A polymer comprising a donor moiety and an acceptor moiety, the electron rich units and the electron poor units being alternately arranged in a polymer backbone, the polymer backbone comprising an alkyl chain having a carbon number N of from 8 to 24, preferably from 10 to 20, more preferably from 12 to 18, and the polymer backbone being conjugated.
2. 2. The polymer of claim 1, wherein the donor moiety comprises a benzodithiazole and the acceptor moiety comprises a substituted dithien.
3. 3. The polymer according to claim 1, wherein the substituent is an alkyl group having a carbon number N of 8 to 24, preferably 9 to 20, more preferably 10 to 15, preferably the substituent is a di-substituent, more preferably the substituent is a di-dodecyl group.
4. 4. A polymer according to claim 3, wherein the polymer comprises 。
5. 5. A targeted nanosystem, characterized in that it comprises an assembly body surface comprising a bis-5-hydroxytryptamine ligand covalently coupled thereto, the assembly body having a hydrophobic organic polymer molecule and a thermally responsive gas prodrug as hydrophobic cores, an amphiphilic biomedical polymer material with good biocompatibility as a carrier, and the hydrophobic organic polymer molecule being the polymer of any one of claims 1-4.
6. 6. The targeted nanosystem of claim 5, wherein the gas comprises hydrogen sulfide, hydrogen selenide, nitric oxide, hydrogen.
7. 7. The targeted nanosystem of claim 5, wherein the thermally responsive gas prodrug comprises 5- (4-hydroxyphenyl) -3H-1, 2-dithiol-3-thione, polyethylenimine-dithiocarbamate, 4-methoxyphenylthiophosphate (morpholine) morpholine salt.
8. 8. The targeted nano system according to claim 5, wherein the biocompatible amphiphilic biomedical polymer material comprises distearoyl phosphatidylethanolamine-polyethylene glycol, polyoxyethylene polyoxypropylene ether, polyethylene glycol-polylactic acid, polyethylene glycol-polycaprolactone, polyethylene glycol-polylactic acid glycolic acid copolymer, the assembly is a co-tissue body, and the co-tissue body comprises a nano probe.
9. 9. Use of a targeted nanosystem according to any one of claims 5-8 for the preparation of a multifunctional thrombolytic nanosystem.
10. 10. The use of claim 9, wherein the multiple functions comprise targeted thrombus recognition, near infrared II-region mediated multi-mode thrombolysis and anti-inflammatory activity.

Description

Polymer, targeting nano system and application thereof Technical Field The invention belongs to the technical field of crossing material chemistry and biomedical tissue engineering materials. In particular, the invention relates to a polymer, a targeting nano system and application thereof, in particular to a photo-thermal and hydrogen sulfide mediated near infrared two-region photo-activated nano polymer material with a synergistic thrombolytic effect, a targeting nano system containing the polymer material and application thereof. Background Thrombotic vascular occlusion is a central pathological mechanism of a variety of life-threatening cardiovascular diseases, including myocardial infarction, ischemic stroke, and pulmonary embolism, and remains a major cause of morbidity and mortality worldwide. Current therapeutic strategies for thrombus management rely primarily on drug thrombolysis, e.g., tissue plasminogen activator (tPA), an FDA approved thrombolytic drug for ischemic stroke treatment. However, the traditional antithrombotic drugs have inherent limitations of short systemic half-life, narrow treatment window, low targeting lesion efficiency, difficulty in penetrating dense fibrin networks of thrombus, and unsatisfactory clinical efficacy. To achieve clinically effective thrombolysis, high doses of drug are often required, which can significantly increase the risk of severe bleeding complications. These limitations highlight the need for innovative, safe and effective strategies to achieve precise and controlled thrombolysis. Non-drug thrombolytic therapy has recently emerged as a promising alternative, with controllable spatiotemporal intervention characteristics hopefully circumventing the safety risks of traditional drugs. Among these methods, photothermal therapy (PTT) enables on-demand thermal activation, promoting fibrin degradation with high precision of localized warming. Of particular interest is phototherapy in the second near infrared region (NIR-II, 1000-1700 nm) is of interest due to its deep tissue penetration, significantly reduced photon scattering, extremely low absorption of endogenous chromophores, and a maximum allowable exposure value (MPE, 1.0W/cm 2 vs 0.33 W/cm2) well above that of near infrared one region (NIR-I, 700-900 nm) illumination. These advantages make NIR-II photothermal therapy an attractive option for safe and efficient light-triggered thrombolytic therapy. Various NIR-II photothermal materials have been explored, including noble metal nanostructures, carbon-based materials, transition metal chalcogenides, organic dyes, and Semiconducting Polymers (SPs). Among them, the semiconductor polymer is favored for its precisely controllable molecular structure, excellent light stability and good biocompatibility, making it an ideal carrier for biomedical photothermal therapy. However, despite rapid research progress, high performance NIR-II region semiconducting polymers with both strong light trapping capability and Gao Guangre conversion efficiency (PCE) are still extremely scarce. Although PTT can achieve precisely controlled heating of the thrombus, pure photothermal ablation may result in incomplete fragmentation of the fibrin network, failing to adequately prevent post-operative re-thrombosis. Thus, a synergistic strategy combining PTT with an adjuvant therapy mechanism is needed to achieve thorough and durable thrombolysis. Hydrogen sulfide (H 2 S) has been noted as an endogenous gas signaling molecule for its multifunctional biological activities including redox regulation, vasodilation, cytoprotection and antiplatelet effects. In the cardiovascular system, H 2 S can not only protect tissues from ischemia reperfusion injury, but also inhibit platelet activation and aggregation, making it an ideal candidate molecule for enhancing PTT-mediated thrombolysis effect and reducing risk of thrombus recurrence. However, the inherent diffusion and rapid oxidation properties of H 2 S severely limit their therapeutic precision, highlighting the urgent need for a controllable, targeted delivery system. On the other hand, efficient penetration into the thrombus site is also critical for thorough thrombolysis. In recent years, nanomotors, nanoscale devices capable of converting chemical or external energy into directed motion, have shown great potential in enhancing drug delivery and improving therapeutic efficiency. Bubble-driven nanomotors are particularly attractive because the bubbles generated by them not only drive the nanomotors in motion, but also enhance thrombolysis efficiency through bubble hydrodynamic effects. Disclosure of Invention The present application aims to overcome the above-mentioned problems and provide a polymer, a targeting nanosystem and use thereof. In one aspect, the present application provides a polymer comprising a donor moiety and an acceptor moiety, alternating electron rich and electron poor units on a polymer backbone, the polymer backbone com