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仿生血小板伪装载药聚吡咯用于精确靶向抗血栓治疗。

Biomimetic platelet-camouflaged drug-loaded polypyrrole for the precise targeted antithrombotic therapy.

机构信息

Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

出版信息

J Nanobiotechnology. 2023 Nov 22;21(1):439. doi: 10.1186/s12951-023-02197-3.

DOI:10.1186/s12951-023-02197-3
PMID:37990207
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10664675/
Abstract

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.

摘要

下肢深静脉血栓形成(LEDVT)会长期影响患者的生活质量,甚至导致肺栓塞,威胁人类健康。目前临床治疗中的抗凝药物由于靶向性差、药物渗透低,存在出血风险。在这里,我们使用血小板(PLT)样生物靶向作用来增强纳米药物在血栓中的传递和积累,降低出血风险。同时,采用“血栓热消融和抗凝”的平行策略来增加血栓中药物的通透性,达到最佳的抗血栓效果。将聚吡咯(PPy)和利伐沙班(Riv,一种抗凝药物)共组装到血小板膜包被的纳米颗粒(NPs)中,即 PLT-PPy/Riv NPs,这些 NPs 可以主动靶向血小板膜中的多个靶点,通过 808nm 激光照射实现热和药物特异性溶栓。与单一光疗或药物治疗相比,该联合治疗在股静脉血栓形成模型中实现了高达 90%的溶栓效果。结果表明,该纳米制剂为远程精确和控制持续溶栓提供了新的方向,符合纳米医学向临床转化的趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/b2d22affbca5/12951_2023_2197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/a191ab666e23/12951_2023_2197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/d9d5502b6e40/12951_2023_2197_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/9627ba9382b8/12951_2023_2197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/eeb8d805393d/12951_2023_2197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/c21afc72e263/12951_2023_2197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/b2d22affbca5/12951_2023_2197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/a191ab666e23/12951_2023_2197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/d9d5502b6e40/12951_2023_2197_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/9627ba9382b8/12951_2023_2197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/eeb8d805393d/12951_2023_2197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/c21afc72e263/12951_2023_2197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c79/10664675/b2d22affbca5/12951_2023_2197_Fig5_HTML.jpg

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