Photo-Controlled Calcium Overload from Endogenous Sources for Tumor Therapy.

Designing reactive calcium-based nanogenerators to produce excess calcium ions (Ca ) in tumor cells is an attractive tumor treatment method. However, nanogenerators that introduce exogenous Ca are either overactive incapable of on-demand release, or excessively inert incapable of an overload of calcium rapidly. Herein, inspired by inherently diverse Ca -regulating channels, a photo-controlled Ca nanomodulator that fully utilizes endogenous Ca from dual sources was designed to achieve Ca 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 Ca nanomodulator can generate reactive oxygen species that stimulate the transient receptor potential ankyrin subtype 1 channel to realize Ca 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 Ca to leak. Both in vitro and in vivo experiments demonstrated that the combination of photo-controlled Ca influx and release could enable Ca overload in the cytoplasm and efficiently inhibit tumor growth.