Polymeric nanocarrier via metabolism regulation mediates immunogenic cell death with spatiotemporal orchestration for cancer immunotherapy

Yichen Guo, Yongjuan Li, Mengzhe Zhang, Rong Ma, Yayun Wang, Xiao Weng, Jinjie Zhang, Zhenzhong Zhang (), Xiaoyuan Chen () and Weijing Yang ()
Additional contact information
Yichen Guo: Zhengzhou University
Yongjuan Li: Zhengzhou University
Mengzhe Zhang: Zhengzhou University
Rong Ma: Zhengzhou University
Yayun Wang: Zhengzhou University
Xiao Weng: Zhengzhou University
Jinjie Zhang: Zhengzhou University
Zhenzhong Zhang: Zhengzhou University
Xiaoyuan Chen: Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore
Weijing Yang: Zhengzhou University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53010-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53010-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53010-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().