AUTHOR=Zhang Xuran , Wang Jian , Feng Qun , Lei Li , Zhu Zhiyong 

TITLE=Manganese-pyrochloric acid photosensitizer nanocomplexes against osteosarcoma: achieving both high activatability and high effectiveness

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=12

YEAR=2025

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2024.1485549

DOI=10.3389/fbioe.2024.1485549

ISSN=2296-4185

ABSTRACT=<sec><title>Introduction</title><p>The application of photodynamic therapy (PDT) is limited by unsatisfactory therapeutic efficacy and dose-dependent phototoxicity in clinical settings. Intravenous nano-drug delivery systems (NDDSs) hold promise for enhancing the delivery efficiency of photosensitive drugs, but often result in aggregation-caused quenching (ACQ) effects, preventing site-specific activation.</p></sec><sec><title>Methods</title><p>We exploited manganese (Mn<sup>2+</sup>)–pyrochloric acid (PPa) nanocomplexes coordinated using the photosensitizer PPa and metal Mn ion for the treatment of osteosarcoma. The nanocomplexes were precisely co-assembled in water to stably co-deliver Mn<sup>2+</sup> and PPa, enabling tumor-specific release and fluorescence recovery.</p></sec><sec><title>Results</title><p>Following laser irradiation, the activated PPa significantly enhanced the killing effects on primary cancer cells. Additionally, Mn<sup>2+</sup> ions activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, promoting maturation of dendritic cells (DCs) and augmenting CD8<sup>+</sup>-mediated antitumor immune responses.</p></sec><sec><title>Discussion</title><p>This study advances the on-demand activation of photosensitive drugs and photodynamic immunotherapy toward clinical applicability by exploiting Mn<sup>2+</sup>–PPa nanocomplexes with high activatability and effectiveness for targeted PDT and immunotherapy.</p></sec>