Immunogenic cell death augmented by manganese zinc sulfide nanoparticles for metastatic melanoma immunotherapy

Z Li, Z Chu, J Yang, H Qian, J Xu, B Chen, T Tian… - ACS …, 2022 - ACS Publications
Z Li, Z Chu, J Yang, H Qian, J Xu, B Chen, T Tian, H Chen, Y Xu, F Wang
ACS nano, 2022ACS Publications
Both T-cell deprivation and insufficient tumor immunogenicity seriously hinder the efficacy of
immune-mediated tumor destruction in melanoma. In this work, an amphiphilic polyethylene
glycol-poly (2-hexoxy-2-oxo-1, 3, 2-dioxaphospholane) copolymer with a thermally sensitive
flowable core (mPEG-b-PHEP) was chosen to incorporate IR780 dye and manganese zinc
sulfide nanoparticles (ZMS) to form polymer micelles (denoted PPIR780-ZMS), which
precisely controlled the release of ZMS after being triggered by near-infrared light (NIR) …
Both T-cell deprivation and insufficient tumor immunogenicity seriously hinder the efficacy of immune-mediated tumor destruction in melanoma. In this work, an amphiphilic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) copolymer with a thermally sensitive flowable core (mPEG-b-PHEP) was chosen to incorporate IR780 dye and manganese zinc sulfide nanoparticles (ZMS) to form polymer micelles (denoted PPIR780-ZMS), which precisely controlled the release of ZMS after being triggered by near-infrared light (NIR). Mn2+-mediated chemodynamic therapy (CDT) by photothermal trigger boosted the generation of reactive oxygen species (ROS), making the PPIR780-ZMS smart bomblets in vivo. It was demonstrated that PPIR780-ZMS could maximize immunogenic cell death (ICD) in cancer, which is characterized by abundant damage-associated molecular pattern (DAMP) exposure. As a result, the cytotoxic T cells (CD8+) and helper T cells (CD4+) expanded and infiltrated the neoplastic foci, which further reprogrammed the suppressive tumor microenvironment (TME) against the primary tumor and pulmonary metastases with safe systemic cytokine expression. In addition, Mn2+-mediated cGAS-STING signaling pathway activation enhanced the antitumor immunity of this nanocomposite, providing a practical strategy for expanding the use of Mn-based nanostructures.
ACS Publications
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