Eph A10-modified pH-sensitive liposomes loaded with novel triphenylphosphine–docetaxel conjugate possess hierarchical targetability and sufficient antitumor effect both in vitro and in vivo

Drug Delivery

Chunrong Yang¹  Jie Li²  Xiuli Zhao³  Dawei Chen³  Menghao Shi³  Shuang Pan³  Mingxi Qiao³  Jiulong Zhang³  Haiyang Hu³ 

[1] College Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, PR China;Mudanjiang Medical University, Mudanjiang, Heilongjiang, PR Chin;School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China;

关键词: pH-responsive;    Docetaxel conjugate;    multifunctional liposomes;    hierarchical targetability;    anticancer efficacy;   

DOI  :  10.1080/10717544.2018.1446475

来源: publisher

【 摘 要 】

Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability. EPSLP/TD was characterized to have a small particle size, high-encapsulation efficiency and excellent pH-sensitive characteristic. Compared with DTX-loaded liposomes (EPSLP/DTX), EPSLP/TD possessed higher cytotoxicity against MCF-7 cell line. Mitochondrial-targeting assay demonstrated mitochondria-targeting moiety triphenylphosphine (TPP) could efficiently deliver DTX to mitochondria. Western immunoblotting assay indicated that EPSLP/TD could efficiently deliver antitumor drug to mitochondria and induce cell apoptosis via mitochondria-mediated apoptosis pathway. In vivo antitumor study demonstrated EPSLP/TD owed excellent in vivo antitumor activity. Histological assay demonstrated EPSLP/TD showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. This work investigated the potential of hierarchical targeting pH-sensitive liposomes is a suitable carrier to activate mitochondria-mediated apoptosis pathway for cancer therapy.

【 授权许可】

CC BY