Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion
Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion
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叶酸结合的纳米气泡通过超声波触发细胞内爆炸选择性地靶向并杀死癌细胞
DOI：
10.1016/j.biomaterials.2018.07.030
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发表时间：
2018
期刊：
影响因子：
14
通讯作者：
Jianping Bin
中科院分区：
文献类型：
--
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
随着癌症靶向纳米技术的快速发展，各种基于纳米粒子的药物递送系统已应用于临床癌症治疗。然而，多重耐药性显着影响治疗效果。物理非药物疗法已成为一种新的、有前途的策略。本研究旨在确定新型叶酸纳米气泡（F-NB）与治疗性超声（US）相结合是否可以作为一种安全有效的物理靶向癌症疗法。使用叶酸缀合的N-棕榈酰壳聚糖（F-PLCS），我们开发了新型F-NB，并表征了它们的理化性质、内化机制、靶向能力、治疗效果和杀伤机制。结果表明，新型 F-NB 通过 FR 与网格蛋白和小窝蛋白介导的体内胞吞作用选择性地积聚在 FR 阳性内皮细胞和肿瘤细胞中。此外，F-NB 在美国照射下通过细胞内爆炸杀死靶细胞。 Hoechst/PI 染色表明细胞凋亡和坏死占体内细胞死亡的很大一部分。 F-NBs 与 US 治疗相结合显着抑制肿瘤生长并提高荷瘤小鼠的总体生存率。在美国的照射下，新型 F-NB 通过细胞内爆炸选择性地杀死体内的 FR 阳性肿瘤细胞，因此是一种有前景的靶向癌症治疗替代方案。
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 endocytosisin vitroandin 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 deathin 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 cellsin vitroandin vivovia intracellular explosion and therefore is a promising alternative for targeted cancer treatment.