脂质过氧化
胶束
化学
单线态氧
纳米载体
光敏剂
激进的
活性成分
细胞毒性
纳米医学
生物物理学
药物输送
光动力疗法
生物化学
药理学
抗氧化剂
体外
有机化学
纳米技术
氧气
材料科学
纳米颗粒
医学
生物
水溶液
作者
Min Gao,Xuan Meng,Xuliang Guo,Jingjing Zhu,Aiping Fan,Zheng Wang,Yanjun Zhao
标识
DOI:10.1016/j.jconrel.2018.08.003
摘要
Traditional antitumor nanomedicines have been suffering from the poor tumor targeting (ca. 1%) by the enhanced permeability and retention (EPR) effect, and the low drug loading (<5%). It was postulated that engineering all-active nanoplatform could increase the therapeutic efficacy to enable the nanocarrier function as both vehicle and active ingredient. To achieve this, a photosensitizer, Ce6 was encapsulated within polymeric micelles with unsaturated fatty acids as the building blocks. Upon light irradiation, the singlet oxygen produced by Ce6 induced lipid peroxidation, resulting in the generation of both active free radicals and aldehydes. These supplementary radicals could exert cytotoxic effect for direct killing tumor cells. The aldehyde end-products induced significant cell cycle arrest at G2 phase in 4T1 cells. The peroxidation process also facilitated the on-demand disassembly of micelles and rapid release of Ce6 to maximize the therapeutic effect of singlet oxygen. These all-active micelles showed a significantly enhanced cytotoxicity with the half maximal inhibitory concentration (IC50) of 0.6 ± 0.2 μg/mL in contrast to the control micelles at 3.4 ± 0.5 μg/mL. The improved antitumor efficacy of the all-active micelles was also demonstrated in the 4T1 tumor-bearing mice in vivo. The current work provides a facile approach to enhance the antitumor efficacy of PDT nanomedicine using the biocompatible fatty acids, which can be applied to various antitumor drugs and unsaturated lipids.
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