Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES

Zhenxiang Fu, Huiping Du, Siyu Meng, Mengjiao Yao, Pan Zhao, Xiang Li, Xinmin Zheng, Zhang Yuan, Hui Yang, Kaiyong Cai, Liangliang Dai

科研成果: 期刊稿件文章同行评审

7 引用 (Scopus)

摘要

The starvation therapy mediated by the lonidamine (LND) was limited by the low drug delivery efficiency, off-target effect and compensative glutamine metabolism. Herein, a hyaluronic acid (HA)-modified reduction-responsive micellar nanosystem co-loaded with glycolysis and glutamine metabolism inhibitor (LND and bis-2-(5-phenylacetmido-1,2,4-thiadiazol-2-yl)ethyl sulfide, BPTES) was constructed for tumor-targeted dual-starvation therapy. The in vitro and in vivo results collectively suggested that the fabricated nanosystem could effectively endocytosed by tumor cells via HA receptor-ligand recognition, and rapidly release starvation-inducers LND and BPTES in response to the GSH-rich intratumoral cytoplasm. Furthermore, the released LND and BPTES were capable of inducing glycolysis and glutamine metabolism suppression, and accompanied by significant mitochondrial damage, cell cycle arrest and tumor cells apoptosis, eventually devoting to the blockade of the energy and substance supply and tumor killing with high efficiency. In summary, HPPPH@L@B nanosystem significantly inhibited the compensatory glycolysis and glutamine metabolism via the dual-starvation therapy strategy, blocked the indispensable energy and substance supply of tumors, consequently leading to the desired tumor starvation and effective tumor killing with reliable biosafety.

源语言英语
文章编号100449
期刊Materials Today Bio
16
DOI
出版状态已出版 - 12月 2022

指纹

探究 'Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES' 的科研主题。它们共同构成独一无二的指纹。

引用此