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This study explores the synergistic potential of PEG-b-P(L-Arg)-based polyion complex micelles (NanoARGs) combined with an immune checkpoint inhibitor (PD-1 antibody) for cancer immunotherapy. Comprehensive experiments, including micelle preparation, in vivo anti-tumor activity evaluation, nitric oxide (NO) quantification, and immunofluorescence analysis, revealed significant insights. NanoARGs exhibited a biphasic effect on tumor growth: high doses inhibited tumor growth through NO generated from liberated Arg, whereas low doses promoted tumor progression. The combination treatment demonstrated significant synergistic anti-tumor activity without notable adverse effects, and treated mice tolerated the regimen well. This approach elevated NO levels in serum and tumor tissues, enhanced immune cell infiltration into tumor tissues, and facilitated the polarization of tumor-associated macrophages to the M1 phenotype. PD-1 antibody further amplified these effects by blocking PD-1/PD-L1 interactions and reactivating T cells. These results underscore the therapeutic potential of this novel approach, providing a foundation for optimizing tumor immunotherapy strategies and advancing clinical applications. Future research will focus on elucidating the mechanisms of action and expanding the scope of this promising treatment.

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• Creative Commons BY Attribution 4.0 International
  

Keyword: nanoparticle-based nitric oxide donor, immune checkpoint inhibitor (PD-1 antibody), cancer immunotherapy, synergistic anti-tumor effect, Poly(L-arginine)-based polymer micelles, Tumor-associated macrophages

Date published: 2025-12-31

Publisher: Taylor & Francis

Journal:

• Science and Technology of Advanced Materials (ISSN: 14686996) vol. 26 2538430

Funding:

Manuscript type: Author's version (Accepted manuscript)

MDR DOI: https://doi.org/10.48505/nims.5621

First published URL: https://doi.org/10.1080/14686996.2025.2538430

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Updated at: 2025-08-01 08:30:21 +0900

Published on MDR: 2025-08-01 08:16:47 +0900