Fenton-like reactions driven by manganese-based nanostructures have been widely applied in cancer treatment owing to the intrinsic physiochemical properties of these nanostructures and their improved sensitivity to the tumor microenvironment. In this work, Zn x Mn 1−x S@polydopamine composites incorporating alloyed Zn x Mn 1−x S and polydopamine (PDA) were constructed, in which the Fenton-like reactions driven by Mn ions can be tuned by a controllable release of Mn ions in vitro and in vivo. As a result, the Zn x Mn 1−x S@PDA exhibited good biocompatibility with normal cells but was specifically toxic to cancer cells. In addition, the shell thickness of PDA was carefully investigated to obtain excellent specific toxicity to cancer cells and promote synergistic chemodynamic and photothermal therapies. Overall, this work highlights an alternative strategy for fabricating high-performance, multifunctional composite nanostructures for a combined cancer treatment.
Specific cytotoxicity for catalytic nanomedicine triggered by the tumor microenvironment (TME) has attracted increasing interest. In this work, we prepared AgBiS 2 hollow nanospheres with narrow bandgaps via rapid precipitation in a weakly polar solvent, which lowered the intrinsic energy gap for the active production of highly reactive hydroxyl radicals ( • OH), especially in the TME. The asprepared AgBiS 2 hollow nanospheres exhibited enhanced optical absorption and high photothermal conversion efficiency (44.2%). In addition, the hollow structured AgBiS 2 nanospheres were found to have a peroxidase-mimicking feature to induce cancer cell-specific cytotoxicity while exhibiting negligible cytotoxicity toward normal cells, which might be attributed to the efficient production of highly reactive • OH originating from the overexpression H 2 O 2 in the TME caused by surface catalysis. In particular, the cancer cell-specific cytotoxicity of the nanospheres was greatly enhanced both in vitro and in vivo upon irradiation with a near-infrared (NIR) laser (808 nm). The above-mentioned features of the hollow structured AgBiS 2 will make it a promising candidate for tumor therapy.
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.
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