Biomimetic polyphenol-coated nanoparticles by Co-assembly of mTOR inhibitor and photosensitizer for synergistic chemo-photothermal therapy.
Biomimetic polyphenol-coated nanoparticles by Co-assembly of mTOR inhibitor and photosensitizer for synergistic chemo-photothermal therapy.
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DOI：
10.1016/j.colsurfb.2021.112177
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
Jing Le;Fang Yang;Mengdie Yin;Ruirui Zhao;Bingchen Zhang;Chao Li;Juanfang Lin;Yifan Fang
中科院分区：
文献类型：
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作者：
Jing Le;Fang Yang;Mengdie Yin;Ruirui Zhao;Bingchen Zhang;Chao Li;Juanfang Lin;Yifan Fang
雷帕霉素（Rapamycin，RAPA）作为一种有效的临床免疫抑制剂，其通过多种途径对多种肿瘤的生长具有显著的抑制作用，尤其是与光热疗法联合应用，正受到越来越多的关注。但其溶解度低、稳定性差的缺点严重制约了其进一步的应用。本文将RAPA、吲哚菁绿色（ICG）和表没食子儿茶素没食子酸酯（EGCG）分别作为化疗药物、光敏剂和仿生涂层，共组装成无载体、高生物相容性的ICG-RAPA-EGCG纳米颗粒（IRE NPs），用于协同癌症治疗。特别地，生物启发的EGCG涂层不仅改善了IRE NPs在生理条件下的稳定性以避免NPs分解和药物释放，而且还保持了ICG的光稳定性以实现优异的光热响应。结果表明，所制备的IRE纳米粒具有良好的单分散性，并在各种储存介质中的稳定性提高。与RAPA或ICG单药相比，IRE纳米粒对MCF-7细胞、HepG 2细胞和HeLa细胞的毒性均呈剂量依赖性，尤其是与近红外激光联合作用时。IRE NPs在H22荷瘤小鼠体内的摄取速度更快，肿瘤部位的蓄积量更高（48 h内），能有效抑制肿瘤生长，且无副作用。总的来说，无载体的IRE纳米颗粒提供了一种简单的替代方法来制造用于组合肿瘤治疗的RAPA/光敏剂共负载的纳米颗粒。
Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.