Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer
Abstract Limited therapeutic options are available for patients with platinum-resistant ovarian cancer (OC). Herein, we developed gallium sulfide-embedded bovine serum albumin nanoformulations (Ga2S3-BSA NMs) with a size of ~ 11 nm via a self-assembly approach. As the nanoformulations degraded in an...
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2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03167-7 |
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| author | Sangsang Tang Yangyang Li Yifeng Fang Mengyan Tu Shenglong Wu Yixuan Cen Junfen Xu |
| author_facet | Sangsang Tang Yangyang Li Yifeng Fang Mengyan Tu Shenglong Wu Yixuan Cen Junfen Xu |
| author_sort | Sangsang Tang |
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| description | Abstract Limited therapeutic options are available for patients with platinum-resistant ovarian cancer (OC). Herein, we developed gallium sulfide-embedded bovine serum albumin nanoformulations (Ga2S3-BSA NMs) with a size of ~ 11 nm via a self-assembly approach. As the nanoformulations degraded in an acidic cancer microenvironment, Ga3+ and H2S gas were simultaneously released to exert their combined anticancer effects. In A2780-CIS and SKOV3-CIS platinum-resistant OC cells, Ga3+ and H2S released from Ga2S3-BSA NMs synergistically enhanced DNA damage, which arrested the cell cycle at S and G2/M phases and suppressed cell proliferation. Meanwhile, Ga2S3-BSA NMs significantly inhibited NF-κB signaling and Bcl2 protein expression, leading to cell apoptosis. Furthermore, Ga2S3-BSA NMs increased cellular lipid peroxidation and triggered ferroptosis. RNA-seq analysis further clarified the comprehensive antitumor mechanisms of Ga2S3-BSA NMs. More importantly, the therapeutic efficacy of Ga2S3-BSA NMs and their ability to enhance the sensitivity to carboplatin and fluzoparib with negligible toxicity were further confirmed in a platinum-resistant OC animal model. Altogether, our results demonstrated a potentially safe and practical strategy by using Ga2S3-BSA NMs to combat drug resistance in platinum-resistant OC. Graphical Abstract |
| format | Article |
| id | doaj-art-a7f06948ab984a408a8ce647c2388f77 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-a7f06948ab984a408a8ce647c2388f772025-02-02T12:41:08ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111810.1186/s12951-025-03167-7Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancerSangsang Tang0Yangyang Li1Yifeng Fang2Mengyan Tu3Shenglong Wu4Yixuan Cen5Junfen Xu6Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of MedicineWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of MedicineDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of MedicineWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of MedicineWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of MedicineDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of MedicineAbstract Limited therapeutic options are available for patients with platinum-resistant ovarian cancer (OC). Herein, we developed gallium sulfide-embedded bovine serum albumin nanoformulations (Ga2S3-BSA NMs) with a size of ~ 11 nm via a self-assembly approach. As the nanoformulations degraded in an acidic cancer microenvironment, Ga3+ and H2S gas were simultaneously released to exert their combined anticancer effects. In A2780-CIS and SKOV3-CIS platinum-resistant OC cells, Ga3+ and H2S released from Ga2S3-BSA NMs synergistically enhanced DNA damage, which arrested the cell cycle at S and G2/M phases and suppressed cell proliferation. Meanwhile, Ga2S3-BSA NMs significantly inhibited NF-κB signaling and Bcl2 protein expression, leading to cell apoptosis. Furthermore, Ga2S3-BSA NMs increased cellular lipid peroxidation and triggered ferroptosis. RNA-seq analysis further clarified the comprehensive antitumor mechanisms of Ga2S3-BSA NMs. More importantly, the therapeutic efficacy of Ga2S3-BSA NMs and their ability to enhance the sensitivity to carboplatin and fluzoparib with negligible toxicity were further confirmed in a platinum-resistant OC animal model. Altogether, our results demonstrated a potentially safe and practical strategy by using Ga2S3-BSA NMs to combat drug resistance in platinum-resistant OC. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03167-7Platinum-resistant ovarian cancerGa2S3-BSA nanoformulationDNA damagePARP inhibitor |
| spellingShingle | Sangsang Tang Yangyang Li Yifeng Fang Mengyan Tu Shenglong Wu Yixuan Cen Junfen Xu Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer Journal of Nanobiotechnology Platinum-resistant ovarian cancer Ga2S3-BSA nanoformulation DNA damage PARP inhibitor |
| title | Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer |
| title_full | Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer |
| title_fullStr | Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer |
| title_full_unstemmed | Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer |
| title_short | Simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo- and PARPi-resistant ovarian cancer |
| title_sort | simultaneously delivery of functional gallium ions and hydrogen sulfide to endow potentiated treatment efficacy in chemo and parpi resistant ovarian cancer |
| topic | Platinum-resistant ovarian cancer Ga2S3-BSA nanoformulation DNA damage PARP inhibitor |
| url | https://doi.org/10.1186/s12951-025-03167-7 |
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