Photo-Controlled Calcium Overload from Endogenous Sources for Tumor Therapy

Jing Jing Hu, Lizhen Yuan, Yunfan Zhang, Jing Kuang, Wen Song, Xiaoding Lou, Fan Xia, Juyoung Yoon

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article numbere202317578
JournalAngewandte Chemie - International Edition
Volume63
Issue number9
DOIs
StatePublished - 26 Feb 2024

Bibliographical note

Publisher Copyright:
© 2024 Wiley-VCH GmbH.

Keywords

  • Calcium Ion Overload
  • Mesoporous Silica Nanoparticles
  • Nitric Oxide
  • TRPA1 Channel
  • Tumor Therapy

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