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工程化由临床批准药物组成的自组装纳米药物用于增强肿瘤纳米治疗

Engineering Self-Assembled Nanomedicines Composed of Clinically Approved Medicines for Enhanced Tumor Nanotherapy.

作者信息

Jiang Quzi, Yu Luodan, Chen Yu

机构信息

Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Nanomaterials (Basel). 2023 Sep 5;13(18):2499. doi: 10.3390/nano13182499.

DOI:10.3390/nano13182499
PMID:37764528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10534536/
Abstract

The traditional nanocarriers are typically constructed to deliver anticancer agents for improving drug bioavailability and enhancing chemotherapeutic efficacy, but this strategy suffers from the critical issue of nanocarrier biosafety that hinders further clinical translation. In this work, a unique nanomedicine (PTX@ICG) has been rationally constructed by combining two clinically approved agents, i.e., paclitaxel (PTX) and indocyanine green (ICG), by a facile ultrasound-assisted self-assembly methodology. The formation of the nanostructure can effectively increase the enrichment of PTX and ICG molecules in the tumor site, and improve the utilization factor of hydrophobic PTX. Moreover, since the molecule interaction in PTX@ICG is mainly Van der Waals forces, the self-assembled structure can be spontaneously dissociated under laser irradiation and release PTX in situ to achieve safe tumor-targeted chemotherapy. Simultaneously, the released ICG can act as photothermic agents for photothermal therapy (PTT), thus combining chemotherapy and PTT to obtain an enhanced tumor nanotherapy via facile self-assembly. The synergistic chemo/photothermal tumor nanotherapy achieved the efficient tumor cell-killing effect and tumor-ablation ability, as systematically demonstrated both in vitro and in vivo. This work provides a distinct paradigm of the self-assembled nanomedicine design for effectively improving the drug bioavailability to achieve high antitumor efficacy.

摘要

传统的纳米载体通常被构建用于递送抗癌药物,以提高药物的生物利用度并增强化疗效果,但这种策略存在纳米载体生物安全性这一关键问题,阻碍了其进一步的临床转化。在这项工作中,通过一种简便的超声辅助自组装方法,将两种临床批准的药物,即紫杉醇(PTX)和吲哚菁绿(ICG),合理构建了一种独特的纳米药物(PTX@ICG)。纳米结构的形成可以有效地增加PTX和ICG分子在肿瘤部位的富集,并提高疏水性PTX的利用效率。此外,由于PTX@ICG中的分子相互作用主要是范德华力,自组装结构在激光照射下可以自发解离并原位释放PTX,以实现安全的肿瘤靶向化疗。同时,释放出的ICG可以作为光热治疗(PTT)的光热剂,从而通过简便的自组装将化疗和PTT相结合,获得增强的肿瘤纳米治疗效果。体内外系统研究均表明,协同化疗/光热肿瘤纳米治疗实现了高效的肿瘤细胞杀伤效果和肿瘤消融能力。这项工作为自组装纳米药物设计提供了一种独特的范例,可有效提高药物生物利用度以实现高抗肿瘤疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/a2fb9946956e/nanomaterials-13-02499-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/4211b7371bb8/nanomaterials-13-02499-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/e0c3cb58ec49/nanomaterials-13-02499-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/de8a29f870f8/nanomaterials-13-02499-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/a2fb9946956e/nanomaterials-13-02499-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/4211b7371bb8/nanomaterials-13-02499-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/e0c3cb58ec49/nanomaterials-13-02499-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/de8a29f870f8/nanomaterials-13-02499-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/10534536/a2fb9946956e/nanomaterials-13-02499-g004.jpg

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