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C 藻蓝蛋白的非共价吲哚菁绿缀合物:制备及肿瘤相关巨噬细胞靶向光热治疗。

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics.

机构信息

College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350116, China.

出版信息

Bioconjug Chem. 2020 May 20;31(5):1438-1448. doi: 10.1021/acs.bioconjchem.0c00139. Epub 2020 Apr 15.

DOI:10.1021/acs.bioconjchem.0c00139
PMID:32255337
Abstract

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.

摘要

多功能近红外(NIR)治疗学纳米平台的构建引起了越来越多的关注。吲哚菁绿(ICG)是一种临床批准的 NIR 荧光成像剂,是一种优秀的光热剂候选物。然而,其稳定性和肿瘤靶向性仍然是其广泛应用的巨大障碍。在这项工作中,C-藻蓝蛋白(CPC)作为肿瘤相关巨噬细胞(TAMs)的靶向载体,通过在水相介质中自组装制备非共价键连接的 CPC-ICG(ICG@CPC)。与游离 ICG 相比,ICG@CPC 在水溶液中以及在光照下具有更好的稳定性,光热转换效率提高了三倍。结果表明,ICG@CPC 可以通过 SR-A 介导的内吞作用选择性地被内化到 J774A.1 细胞中,并导致对 J774A.1 细胞的光毒性增强。结果表明,与单独使用 ICG 相比,ICG@CPC 显著提高了药物在肿瘤中的积累和光热治疗效果。本研究首次利用 CPC 作为 ICG 的 TAMs 靶向纳米载体,可能会促进进一步合理设计基于 ICG 的光热纳米药物,以实现精确高效的癌症治疗。

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