Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery

Pei Wei Shueng, Lu Yi Yu, Hsiao Hsin Hou, Hsin Cheng Chiu, Chun Liang Lo*

*此作品的通信作者

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer–liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were de-signed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer–liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery.

原文English
文章編號3080
期刊International Journal Of Molecular Sciences
23
發行號6
DOIs
出版狀態Published - 1 3月 2022

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