White-light-driven fluorescence switch for super-resolution imaging guided photodynamic and photoacid therapy

Photocaged fluorophores with photoactivatable characteristics presented important applications in imaging the biological structures and processes.Taking advantage of their super-resolution imaging merits to manipulate and visualize anti-cancer treatment is always a goal of modern clinical medicine.Traditional photodynamic therapy(PDT) is a noninvasive treatment but limited in intracellular oxygen content.Type I PDT and photoacid therapy(PAT) are two effective supplements of traditional PDT especially in hypoxic condition.Herein,a novel white-light-driven fluorescence switch(7H-dibenzo[c,g]carbazol-7-yl)(2-iodophenyl)methanone(2IB) was designed and synthesized as an unprecedent “all in one” platform for stochastic optical reconstruction microscopy(STORM) imaging guided Type Ⅰ/Ⅱ PDT and PAT.The experimental and theoretical studies revealed that the working mechanism is based on two competing paths under excitation:photosensitization and photocyclization reaction.Efficient intersystem crossing(ISC) ensured the generation of reactive oxygen species(ROS) for PDT,while low energy barrier facilitated the photocyclization reaction that simultaneously yielded emissive fluorophores(2IBC) and H^(+) for super-resolution imaging and photoacid,respectively.Impressively,the fluorescent intensity of mitochondria-targeted 2IBC was positively correlated with treatment efficacy,which is beneficial to spatiotemporally visualized therapeutic process and outcome.As a result,superior anti-tumor performance was achieved in vitro and in vivo.This contribution provided a multifunctional nanodrug paradigm for multimode cancer diagnosis and treatment.