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负载吲哚菁绿与尿激酶非共价复合物的环状RGD功能化聚乳酸-羟基乙酸共聚物纳米颗粒用于协同溶栓

Cyclic RGD functionalized PLGA nanoparticles loaded with noncovalent complex of indocyanine green with urokinase for synergistic thrombolysis.

作者信息

Zhang Sha, Li Jinjie, Ren Jiefeng, Xue Zaiyao, Qi Xinlian, Si Quanjin

机构信息

Department of Geriatric Cardiology, Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, China.

Medical School of Chinese PLA, Beijing, China.

出版信息

Front Bioeng Biotechnol. 2022 Aug 10;10:945531. doi: 10.3389/fbioe.2022.945531. eCollection 2022.

DOI:10.3389/fbioe.2022.945531
PMID:36032719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9399888/
Abstract

Thrombotic diseases have the characteristics of long latency period, rapid onset, and high mortality rate, which seriously threaten people's life and health. The aim of this research is to fabricate a novel indocyanine green complex of urokinase (ICG@uPA) and employ the amphiphilic PEG-PLGA polymer to deliver the complex as an enzyme-phototherapeutic synergistic thrombolysis platform. The noncovalent indocyanine green (ICG) complex of urokinase (ICG@uPA) was prepared supramolecular self-assembly and then encapsulated into cRGD decorated polymeric nanoparticles (cRGD-ICG-uPA NPs) by double-emulsion solvent evaporation method. Then the nanoparticles (NPs) were characterized in terms of particle size, optical properties, release, etc. The targeting and thrombolytic effect of the nanoparticles were studied both and . ICG@uPA and cRGD-ICG-uPA NPs displayed significantly higher photostability and laser energy conversion efficiency than free ICG. Concomitantly, the NPs exhibited selective binding affinity to the activated platelets and specific accumulation in the mouse mesenteric vessel thrombus. Significant thrombolysis was achieved by photo-assisted synergistic therapy with reduced dose and systemic bleeding risk of uPA. Our results prove that the functional PLGA nanoparticle loaded with the ICG@uPA offers a novel option for effective and safe thrombolytic treatment.

摘要

血栓性疾病具有潜伏期长、发病迅速、死亡率高的特点，严重威胁着人们的生命健康。本研究的目的是制备一种新型的尿激酶吲哚菁绿复合物（ICG@uPA），并利用两亲性PEG-PLGA聚合物将该复合物作为酶-光疗协同溶栓平台进行递送。通过超分子自组装制备了尿激酶的非共价吲哚菁绿（ICG）复合物（ICG@uPA），然后采用双乳液溶剂蒸发法将其包裹在cRGD修饰的聚合物纳米颗粒（cRGD-ICG-uPA NPs）中。随后对纳米颗粒（NPs）的粒径、光学性质、释放等进行了表征。同时研究了纳米颗粒的靶向性和溶栓效果。ICG@uPA和cRGD-ICG-uPA NPs表现出比游离ICG显著更高的光稳定性和激光能量转换效率。与此同时，这些纳米颗粒对活化血小板表现出选择性结合亲和力，并在小鼠肠系膜血管血栓中特异性聚集。通过光辅助协同治疗，以降低剂量的尿激酶实现了显著的溶栓效果，同时降低了全身出血风险。我们的结果证明，负载ICG@uPA的功能性PLGA纳米颗粒为有效且安全的溶栓治疗提供了一种新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/778b4b4e6128/fbioe-10-945531-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/a35085b6c852/fbioe-10-945531-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/d134a9bc9601/fbioe-10-945531-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/c82e1c0ecf56/fbioe-10-945531-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/4f104b2c58f5/fbioe-10-945531-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/9566008141bc/fbioe-10-945531-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/109f9d5ba10b/fbioe-10-945531-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/9af9126b28c8/fbioe-10-945531-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/778b4b4e6128/fbioe-10-945531-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/a35085b6c852/fbioe-10-945531-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/d134a9bc9601/fbioe-10-945531-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/c82e1c0ecf56/fbioe-10-945531-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/6bd250fe017e/fbioe-10-945531-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/4f104b2c58f5/fbioe-10-945531-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/9566008141bc/fbioe-10-945531-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/109f9d5ba10b/fbioe-10-945531-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/9af9126b28c8/fbioe-10-945531-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9399888/778b4b4e6128/fbioe-10-945531-g009.jpg

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