Adipocytes as Anticancer Drug Delivery Depot

Autor: Jennifer Soto, Guojun Chen, Gianpietro Dotti, Peter Abdou, Zejun Wang, Di Wen, Denis Fourches, Yuqi Zhang, Qian Chen, Ming Liu, Song Li, Jinqiang Wang, Masao Ohashi, George Van Den Driessche, Zhen Gu, Hongjun Li, Quanyin Hu
Rok vydání: 2019
Předmět:
Zdroj: Matter. 1:1203-1214
ISSN: 2590-2385
Popis: Summary Tumor-associated adipocytes promote tumor growth by providing energy and causing chronic inflammation. Here, we have exploited the lipid metabolism to engineer adipocytes that serve as a depot to deliver cancer therapeutics at the tumor site. Rumenic acid (RA), as an anticancer fatty acid, and a doxorubicin prodrug (pDox) with a reactive oxygen species (ROS)-cleavable linker, are encapsulated in adipocytes to deliver therapeutics in a tumor-specific bioresponsive manner. After intratumoral or postsurgical administration, lipolysis releases the RA and pDox that is activated by intracellular ROS-responsive conversion, subsequently promoting antitumor efficacy. Furthermore, downregulation of PD-L1 expression is observed in tumor cells, favoring the emergence of CD4+ and CD8+ T cell-mediated immune responses.
Databáze: OpenAIRE