Hydrogen peroxide-activatable iodoBodipy-phthalhydrazid conjugate nanoparticles for cancer therapy

The dependence on outer light source strongly hinders clinical applications of photodynamic therapy (PDT) to the deep-seated tumor. However, the majority of documented PDT systems that function without the external light source rely on either the chemiluminescence resonance energy transfer (CRET) or fluorescence resonance energy transfer (FRET) mechanism, which decreases the energy transfer efficiency and reproducibility of PDT. Herein, we developed a novel single-molecule triplet photosensitizer (iodoBodipy (IBDP)-L) that can be chemiexcited to triplet excited state to generate reactive oxygen species instead of outer light irradiation. The direct bonding of phthalhydrazid moiety to iodoBodipy fluorophore evoked valid intramolecular energy transfer (IET), and once phthalhydrazid part is activated by hydrogen peroxide, the released reaction energy could excite the iodoBodipy-phthalhydrazid conjugate as a whole. Reaction product IBDP-L-COOH showed high triplet state quantum yield (f(T) = 65%) and large spin-orbit coupling. A large amount of reactive oxygen species (ROS) was produced in MCF-7 cells, thus inhibiting the cell growth both in vitro and in vivo after IBDP-L was formulated into nanoparticles (NPs) via nanoprecipitation. We believe that the synthesized IodoBodipy-phthalhydrazid conjugate based on the IET mechanism will open a new door in the molecular design of efficient triplet photosensitizers for treating deeply seated tumors in the future.