PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors
Abstract Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach dev...
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2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03094-7 |
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| author | Lan Zou Rujing Wang Mengnan Zhao Yuke Li Chen Sun Jinjin Xie Yan Chen Qian Jing Dandan Mi Sanjun Shi |
| author_facet | Lan Zou Rujing Wang Mengnan Zhao Yuke Li Chen Sun Jinjin Xie Yan Chen Qian Jing Dandan Mi Sanjun Shi |
| author_sort | Lan Zou |
| collection | DOAJ |
| description | Abstract Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach devoid of any chemical alterations to develop a novel photosensitizer called “pharmaceutical-dots (pharm-dots)” by combining nonemissive polymers (Poly (lactic-co-glycolic acid), PLGA) with nonfluorescent invisible molecules like curcumin, berberine, oridonin into PLGA nanoparticles (PLGA-NPs). Initially, our research commenced with a comprehensive mechanistic comparison study, consolidating fragmented information on optical mechanisms. This exploration revealed that surface passivation atoms play a dominant role in governing the fluorescence emission of PLGA-NPs. Remarkably, these new luminophores, composed of two non-inherently luminous components, exhibit a remarkable synergistic boost in photoluminescence through a “0 + 0 > 2” phenomenon. In-depth investigations uncovered that these luminous PLGA-NPs, capable of generating 1O2, induce pyroptosis under photoexcitation conditions through the caspase-3/gasdermin E (GSDME) pathway. Simultaneously, our findings highlight PLGA-NPs as a novel optical formulation suitable for imaging, displaying substantial biological activity when paired with photoirradiation. This discovery holds the potential to facilitate the application of light-controlled pyroptosis in antitumor therapy, marking a promising stride toward innovative approaches in cancer treatment. Graphical abstract |
| format | Article |
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| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-93ca0b718aec4e80bcca4ae283021b6d2025-01-26T12:50:54ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112310.1186/s12951-025-03094-7PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumorsLan Zou0Rujing Wang1Mengnan Zhao2Yuke Li3Chen Sun4Jinjin Xie5Yan Chen6Qian Jing7Dandan Mi8Sanjun Shi9State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineSchool of Basic Medical Sciences, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese MedicineAbstract Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach devoid of any chemical alterations to develop a novel photosensitizer called “pharmaceutical-dots (pharm-dots)” by combining nonemissive polymers (Poly (lactic-co-glycolic acid), PLGA) with nonfluorescent invisible molecules like curcumin, berberine, oridonin into PLGA nanoparticles (PLGA-NPs). Initially, our research commenced with a comprehensive mechanistic comparison study, consolidating fragmented information on optical mechanisms. This exploration revealed that surface passivation atoms play a dominant role in governing the fluorescence emission of PLGA-NPs. Remarkably, these new luminophores, composed of two non-inherently luminous components, exhibit a remarkable synergistic boost in photoluminescence through a “0 + 0 > 2” phenomenon. In-depth investigations uncovered that these luminous PLGA-NPs, capable of generating 1O2, induce pyroptosis under photoexcitation conditions through the caspase-3/gasdermin E (GSDME) pathway. Simultaneously, our findings highlight PLGA-NPs as a novel optical formulation suitable for imaging, displaying substantial biological activity when paired with photoirradiation. This discovery holds the potential to facilitate the application of light-controlled pyroptosis in antitumor therapy, marking a promising stride toward innovative approaches in cancer treatment. Graphical abstracthttps://doi.org/10.1186/s12951-025-03094-7PyroptosisPhotosensitizerPLGANonfluorescent invisible moleculesPharm-dots |
| spellingShingle | Lan Zou Rujing Wang Mengnan Zhao Yuke Li Chen Sun Jinjin Xie Yan Chen Qian Jing Dandan Mi Sanjun Shi PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors Journal of Nanobiotechnology Pyroptosis Photosensitizer PLGA Nonfluorescent invisible molecules Pharm-dots |
| title | PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors |
| title_full | PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors |
| title_fullStr | PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors |
| title_full_unstemmed | PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors |
| title_short | PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors |
| title_sort | plga confers upon conventional nonfluorescent molecules luminescent properties to trigger 1o2 induced pyroptosis and immune response in tumors |
| topic | Pyroptosis Photosensitizer PLGA Nonfluorescent invisible molecules Pharm-dots |
| url | https://doi.org/10.1186/s12951-025-03094-7 |
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