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Angew. Chem.-Int. Edit., Jan 08 2024, | https://doi.org/10.1002/anie.202317578
Photo-Controlled Calcium Overload from Endogenous Sources for Tumor Therapy
Jing-Jing Hu 1, Lizhen Yuan 1, Yunfan Zhang 1, Jing Kuang 2, Wen Song 3, Xiaoding Lou 1, Fan Xia 1, Juyoung Yoon 4
1China University of Geosciences, Material Science and Chemistry, CHINA.
2Huazhong University of Science and Technology, Tonji Medical College, CHINA.
3Hainan University, Biomedical Engineering, CHINA.
4Ewha Womans University, Department of Chemistry, 11-1 Daehyun-Dong, Seodaemun-Gu, 120-750, Seoul, KOREA, REPUBLIC OF.
CORRESPONDING AUTHOR : Juyoung Yoon
Abstract
Designing reactive calcium-based nanogenerators to produce excess calcium ions (Ca2+) in tumor cells is an attractive tumor treatment method. However, nanogenerators that introduce exogenous Ca2+ are either overactive incapable of on-demand release, or excessively inert incapable of an overload of calcium rapidly. Herein, inspired by inherently diverse Ca2+-regulating channels, a photo-controlled Ca2+ nanomodulator that fully utilizes endogenous Ca2+ from dual sources was designed to achieve Ca2+ overload in tumor cells. Specifically, mesoporous silica nanoparticles were used to co-load bifunctional indocyanine green as a photodynamic/photothermal agent and a thermal-sensitive nitric oxide (NO) donor (BNN-6). Thereafter, they were coated with hyaluronic acid, which served as a tumor cell-targeting unit and a gatekeeper. Under near-infrared light irradiation, the Ca2+ nanomodulator can generate reactive oxygen species that stimulate the transient receptor potential ankyrin subtype 1 channel to realize Ca2+ influx from extracellular environments. Simultaneously, the converted heat can induce BNN-6 decomposition to generate NO, which would open the ryanodine receptor channel in the endoplasmic reticulum and allow stored Ca2+ to leak. Both in vitro and in vivo experiments demonstrated that the combination of photo-controlled Ca2+ influx and release could enable Ca2+ overload in the cytoplasm and efficiently inhibit tumor growth.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-01-23)
- 국내(교신)+국외 연구진
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