Manganese-pyrochloric acid photosensitizer nanocomplexes against osteosarcoma: achieving both high activatability and high effectiveness
IntroductionThe 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 resu...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1485549/full |
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| Summary: | IntroductionThe 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.MethodsWe exploited manganese (Mn2+)–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 Mn2+ and PPa, enabling tumor-specific release and fluorescence recovery.ResultsFollowing laser irradiation, the activated PPa significantly enhanced the killing effects on primary cancer cells. Additionally, Mn2+ ions activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, promoting maturation of dendritic cells (DCs) and augmenting CD8+-mediated antitumor immune responses.DiscussionThis study advances the on-demand activation of photosensitive drugs and photodynamic immunotherapy toward clinical applicability by exploiting Mn2+–PPa nanocomplexes with high activatability and effectiveness for targeted PDT and immunotherapy. |
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| ISSN: | 2296-4185 |