Two-photon activated-photodynamic therapy (TPA-PDT) allows for spatially selective treatment of cancers, and enhances the tissue penetration depth of incident light. The three dimensional (3D) interface energy transfers in hexagonal mesoporous silica nanoparticles (MSNs) can significantly enhance the photodynamic effect. By providing a well-defined mesoporous nanostructure, we established an efficient and controllable energy transfer mechanism via the facile modification of a two-photon antenna molecule and photosensitizer on different topological domains in the MSN. The cytotoxicity induced by the singlet oxygen, generated following relay of energy transfer, was demonstrated in both in vitro and in vivo breast cancer models. Therefore, our results contribute new insight to the highly efficient energy transfer within a single nanoparticle for two-photon activated PDT, worthwhile for studying its potential for development in clinical translation.
