Ding Li, Yu Xinghua, Cai Shihao, Mahmood Azhar, Meng Wenjing, Liu Xiaotong, Liu Jiahan, Li Jieyun, Zhang Xuejuan, Wu Chuanbin
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
Int J Pharm. 2025 Jan 25;669:125093. doi: 10.1016/j.ijpharm.2024.125093. Epub 2024 Dec 17.
The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of BiSe nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking. Our findings reveal that the cRGD-coated BiSe nanofoams are internalized through three distinct endocytosis pathways: Rab34-mediated macropinocytosis, caveolae-dependent, and clathrin-dependent endocytosis. These nanofoams then accumulate in lysosomes via autophagy. Furthermore, inhibiting exocytosis reduces the loss of these nanofoams from cancer cells, enhancing photothermal and chemotherapy effects. This exocytosis-inhibiting strategy demonstrates significant potential for cancer therapy, validated by successful in vitro and in vivo results.
用于光热治疗纳米平台的cRGD肽表面涂层策略在开发安全有效的癌症治疗方法方面显示出巨大潜力。然而，由于细胞内运输和纳米-生物相互作用的复杂性，这些平台的确切细胞内机制仍不清楚。本研究调查了一种代表性的光热治疗纳米平台——BiSe纳米泡沫在癌细胞中与cRGD肽涂层的纳米-生物相互作用，重点关注内吞作用、胞吐作用和细胞运输。我们的研究结果表明，cRGD涂层的BiSe纳米泡沫通过三种不同的内吞途径内化：Rab34介导的巨胞饮作用、小窝蛋白依赖性和网格蛋白依赖性内吞作用。然后这些纳米泡沫通过自噬在溶酶体中积累。此外，抑制胞吐作用可减少这些纳米泡沫从癌细胞中的损失，增强光热和化疗效果。这种抑制胞吐作用的策略在癌症治疗中显示出巨大潜力，体外和体内实验结果均验证了这一点。
