Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy
Abstract Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we cons...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02220-7 |
| _version_ | 1827590368767508480 |
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| author | Chenglong Wang Tao Li Zhen Wang Yao Li Yan Liu Maochang Xu Zongquan Zhang Yiping Deng Liang Cai Chunxiang Zhang Chunhong Li |
| author_facet | Chenglong Wang Tao Li Zhen Wang Yao Li Yan Liu Maochang Xu Zongquan Zhang Yiping Deng Liang Cai Chunxiang Zhang Chunhong Li |
| author_sort | Chenglong Wang |
| collection | DOAJ |
| description | Abstract Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. Graphical Abstract |
| first_indexed | 2024-03-09T01:15:54Z |
| format | Article |
| id | doaj.art-b5ca037b514847c5929affdc4e2b3fd1 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T01:15:54Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-b5ca037b514847c5929affdc4e2b3fd12023-12-10T12:30:26ZengBMCJournal of Nanobiotechnology1477-31552023-12-0121111910.1186/s12951-023-02220-7Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapyChenglong Wang0Tao Li1Zhen Wang2Yao Li3Yan Liu4Maochang Xu5Zongquan Zhang6Yiping Deng7Liang Cai8Chunxiang Zhang9Chunhong Li10Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Sichuan ProvinceDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Science and Technology, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityNuclear Medicine Department of the First Affiliated Hospital, Southwest Medical UniversityThe Key Laboratory of Medical Electrophysiology of the Ministry of Education, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityAbstract Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. Graphical Abstracthttps://doi.org/10.1186/s12951-023-02220-7Mitochondrial Ca2+ overloadPhotothermal therapyBreast cancerCurcuminIndocyanine green |
| spellingShingle | Chenglong Wang Tao Li Zhen Wang Yao Li Yan Liu Maochang Xu Zongquan Zhang Yiping Deng Liang Cai Chunxiang Zhang Chunhong Li Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy Journal of Nanobiotechnology Mitochondrial Ca2+ overload Photothermal therapy Breast cancer Curcumin Indocyanine green |
| title | Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy |
| title_full | Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy |
| title_fullStr | Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy |
| title_full_unstemmed | Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy |
| title_short | Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy |
| title_sort | nano modulators with the function of disrupting mitochondrial ca2 homeostasis and photothermal conversion for synergistic breast cancer therapy |
| topic | Mitochondrial Ca2+ overload Photothermal therapy Breast cancer Curcumin Indocyanine green |
| url | https://doi.org/10.1186/s12951-023-02220-7 |
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