Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion

作者：Shuxin Shen, Ying Li, Yunbin Xiao, Zonglei Zhao, Chuanxi Zhang, Junfen Wang, Hairui Li, Feng Liu, Nvqin He, Ye Yuan, Yongkang Lu, Shengcun Guo, Yan Wang, Wangjun Liao, Yulin Liao, Yanmei Chen, Jianping Bin · 发表于：Biomaterials · 年份：2018 · DOI：10.1016/j.biomaterials.2018.07.030 · 被引用次数：64 · 研究领域：Nanoplatforms for cancer theranostics、Ultrasound and Hyperthermia Applications、Nanoparticle-Based Drug Delivery

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.