Targeted Reprogramming of Vitamin B3 Metabolism as a Nanotherapeutic Strategy towards Chemoresistant Cancers

Targeted Reprogramming of Vitamin B3 Metabolism as a Nanotherapeutic Strategy towards Chemoresistant Cancers

© 2023 Wiley-VCH GmbH.

Détails bibliographiques
Publié dans:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 36 vom: 13. Sept., Seite e2301257
Auteur principal: Guo, Daoxia (Auteur)
Autres auteurs: Ji, Xiaoyuan, Xie, Hui, Ma, Jia, Xu, Chunchen, Zhou, Yanfeng, Chen, Nan, Wang, Hui, Fan, Chunhai, Song, Haiyun
Format: Article en ligne
Langue:English
Publié: 2023
Accès à la collection:Advanced materials (Deerfield Beach, Fla.)
Sujets:Journal Article cancer-associated fibroblast remodeling chemoresistant cancers gemini-like nanoparticles hydrogels vitamin B3 metabolic reprogramming Antineoplastic Agents Vitamins
Description
Résumé:© 2023 Wiley-VCH GmbH.
Cancer-associated fibroblasts (CAFs) promote cancer stem cell (CSC)-mediated chemoresistance and immunosuppressive tumor microenvironment. However, direct depletion of CAFs may increase cancer invasiveness and metastasis. As a generalized strategy against chemoresistant cancers, Gemini-like homotypic targeting nanoparticles (NPs) are designed for two-pronged CAF transformation and cancer cell elimination. The CAF-targeted NPs couple vitamin B3 metabolic reprogramming to epigenetic modulation of secreted pro-stemness and immunosuppressive factors, thereby diminishing CSC and suppressive immune cell populations to enhance cancer cell drug susceptibility and cytotoxic T cell infiltration. In mouse models of breast, liver, pancreatic and colorectal cancers that are resistant to their respective first-line chemotherapeutics, a single dose of hydrogel co-delivering the Gemini-like NPs can rehabilitate chemosensitivity, induce immune activation, and achieve tumor regression. Moreover, it stimulates robust T cell memory for long-term protection against tumor rechallenge. This study thus represents an innovative approach with broad applicability for overcoming cancer chemoresistance
Description:Date Completed 08.09.2023
Date Revised 08.09.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202301257