Dendritic Polymer-Based Nanomedicines Remodel the Tumor Stroma : Improve Drug Penetration and Enhance Antitumor Immune Response
© 2024 Wiley‐VCH GmbH.
| Publié dans: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 25 vom: 01. Juni, Seite e2401304 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2024
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| Accès à la collection: | Advanced materials (Deerfield Beach, Fla.) |
| Sujets: | Journal Article ECM regulation antitumor immune response cancer‐associated fibroblasts dendritic polymer‐based nanomedicines drug penetration Antineoplastic Agents Dendrimers Drug Carriers |
| Résumé: | © 2024 Wiley‐VCH GmbH. The dense extracellular matrix (ECM) in solid tumors, contributed by cancer-associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy of remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote penetration of an immunogenic cell death (ICD) inducer (epirubicin, Epi) via apoptotic vesicles, ultimately enhancing the treatment efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-based nanomedicines (poly[OEGMA-Dendron(G2)-Gly-Phe-Leu-Gly-DAS] (P-DAS) and poly[OEGMA-Dendron(G2)-hydrazone-Epi] (P-Epi)) are developed for sequential delivery of DAS and Epi, respectively. P-DAS reprograms CAFs to reduce collagen by downregulating collagen anabolism and energy metabolism, thereby reducing the ECM deposition. The regulated ECM can enhance tumor penetration of P-Epi to strengthen its ICD effect, leading to an amplified antitumor immune response. In breast cancer-bearing mice, this approach alleviates the ECM barrier, resulting in reduced tumor burden and increased cytotoxic T lymphocyte infiltration, and more encouragingly, synergizes effectively with anti-programmed cell death 1 (PD-1) therapy, significantly inhibiting tumor growth and preventing lung metastasis. Furthermore, systemic toxicity is barely detectable after sequential treatment with P-DAS and P-Epi. This approach opens a new avenue for treating desmoplastic tumors by metabolically targeting CAFs to overcome the ECM barrier |
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| Description: | Date Completed 20.06.2024 Date Revised 20.07.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202401304 |