Tumor Microenvironment-Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy

Tumor Microenvironment-Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 6 vom: 08. Feb., Seite e2304845
1. Verfasser: Liu, Dan (VerfasserIn)
Weitere Verfasser: Liang, Shuang, Ma, Kongshuo, Meng, Qian-Fang, Li, Xingang, Wei, Jian, Zhou, Mengli, Yun, Kaiqing, Pan, Yuanwei, Rao, Lang, Chen, Xiaoyuan, Wang, Zhaohui
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article STING pathway TLR4 pathway cancer immunotherapy nanoparticles tumor microenvironment Toll-Like Receptor 4
Beschreibung
Zusammenfassung:© 2023 Wiley-VCH GmbH.
Insufficient activation of the stimulator of interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits the effect of cancer immunotherapy. Herein, tumor microenvironment (TME)-responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING and Toll-like receptor 4 (TLR4) to augment STING activation via TLR4-mediated nuclear factor-kappa B signaling pathway stimulation, leading to the increased secretion of type I interferons (i.e., 4.0-fold enhancement of IFN-β) and pro-inflammatory cytokines to promote a specific T cell immune response. Moreover, PMM NPs relieve the immunosuppression of the TME by decreasing the percentage of regulatory T cells, and polarizing M2 macrophages to the M1 type, thus creating an immune-supportive TME to unleash a cascade adaptive immune response. Combined with an anti-PD-1 antibody, synergistic efficacy is achieved in both inflamed colorectal cancer and noninflamed metastatic breast tumor models. Moreover, rechallenging tumor-free animals with homotypic cells induced complete tumor rejection, indicating the generation of systemic antitumor memory. These TME-responsive nanoparticles may open a new avenue to achieve the spatiotemporal orchestration of STING activation, providing a promising clinical candidate for next-generation cancer immunotherapy
Beschreibung:Date Completed 09.02.2024
Date Revised 09.02.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202304845