Mitochondrial targeted drug delivery combined with manganese catalyzed Fenton reaction for the treatment of breast cancer

Xincheng Zhong, Xiaoyan Bao, Haiqing Zhong, Yi Zhou, Zhentao Zhang, Yiying Lu, Qi Dai, Qiyao Yang, Peng Ke, Yiyi Xia, Linjie Wu, Zaiyun Sui, Yan Lu, Min Han, WenHong Xu, Jianqing Gao

Journal:INTERNATIONAL JOURNAL OF PHARMACEUTICS

IF:6.51

DOI:10.1016/j.ijpharm.2022.121810

PMID:35580685

Published:2022-05-14

research field:神经科学纳米毒理学细胞生物学环境毒理学

Abstract

In previous studies, we found that triphenylphosphine-modified doxorubicin (TPP-DOX) can effectively kill drug-resistant tumor cells, but its effect on sensitive tumor cells is weakened. In this research, with albumin from Bovine Serum (BSA) as a carrier, [email protected] ( [email protected] ) nanoparticles were prepared by co-loading TPP-DOX and manganese which can realize the combination of chemotherapy and chemodynamic therapy (CDT). The uniform and stable nano-spherical nanoparticle can promote drug uptake, achieve mitochondrial-targeted drug delivery, increase intracellular reactive oxygen species (ROS) and catalyze the production of highly toxic oxidative hydroxyl radicals (OH·), further inhibiting the growth of both sensitive and drug-resistant MCF-7 cells. Besides, [email protected] can down-regulate the stemness-related proteins and the metastasis-related proteins, potentially decreasing the tumor stemness and metastasis. In vivo experiment indicated that [email protected] was able to exert desired antitumor effect, good tumor targeting and biocompatibility .

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