Targeted Reprogramming of Vitamin B3 Metabolism as a Nanotherapeutic Strategy towards Chemoresistant Cancers
© 2023 Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 36 vom: 13. Sept., Seite e2301257 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article cancer-associated fibroblast remodeling chemoresistant cancers gemini-like nanoparticles hydrogels vitamin B3 metabolic reprogramming Antineoplastic Agents Vitamins |
| Zusammenfassung: | © 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 |
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| Beschreibung: | Date Completed 08.09.2023 Date Revised 08.09.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202301257 |