Immunogenic Cell Death Augmented by Manganese Zinc Sulfide Nanoparticles for Metastatic Melanoma Immunotherapy

Abstract

Both T-cell deprivation and insufficient tumor immunogenicity seriously hinder the efficacy of immunemediated 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 PP IR780-ZMS ), which precisely controlled the release of ZMS after being triggered by nearinfrared light (NIR). Mn 2+ -mediated chemodynamic therapy (CDT) by photothermal trigger boosted the generation of reactive oxygen species (ROS), making the PP IR780-ZMS smart bomblets in vivo. It was demonstrated that PP IR780-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, Mn 2+ -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.

Targeting Proinflammatory Molecules Using Multifunctional MnO Nanoparticles to Inhibit Breast Cancer Recurrence and Metastasis

“…MnO@curcumin@IR780 nanoparticles exhibited a broad absorption band (∼600–800 nm) and an obvious PL peak at ∼780 nm, which was attributed to IR780, demonstrating the successful decoration of IR780 on the MnO@curcumin nanoparticles. In comparison to IR780, the broadening absorption bands and shifting emission peaks of MnO@curcumin@IR780 nanoparticles might be attributed to the hydrophobic interaction and the changes in solvent polarity, as well as molecular interactions between IR780 and MnO@curcumin nanoparticles, a finding well consistent with previous reports. ,− The increased hydrodynamic size, altered absorption/PL spectra, and color change of the samples suggested that MnO (MnO@curcumin) nanoparticles were successfully functionalized with curcumin (IR780).…”

Ultrasmall zirconium carbide nanodots for synergistic photothermal-radiotherapy of glioma

“…All staining was conducted according to the corresponding standard experimental protocols. 48 All images of tissue slides were acquired by the Tissue FAXS Plus S system (TissueGnostics GmbH, Austria).…”

Terminalia chebula Polyphenol and Near-Infrared Dye-Loaded Poly(lactic acid) Nanoparticles for Imaging and Photothermal Therapy of Cancer Cells

“…The polymeric system is introduced along with the addition of IR-775 dye for better uptake and entrapment of polyphenols into the hydrophobic cores, resulting in a self-assembled nano-carrier system for profound drug delivery . Some studies have shown that the uptake of hydrophobic moieties in the polymeric nanosystem participates in structural, metabolic, and signaling pathways that target cancer cells, promoting cell death through up-/down-regulation of signaling pathways. , The presence of hydrophobic fluorescent IR-775 dye in the nanosystem enhances the uptake of active polyphenol molecules to achieve maximum yield when encapsulated with PLA . Herein, we report that P p IR NPs can serve as multifunctional nanosystems for bioimaging and be used for commingled PDT/PTT upon validation.…”