Biotin receptor and mitochondria dual targeted AIE photosensitizer for fluorescence imaging guided photodynamic anticancer therapy

[Display omitted] •Four organic photosensitizers with AIE characteristic were developed.•TSPy-B exhibited excellent ROS (type I and type II) generation ability.•TSPy-B showed biotin receptor and mitochondria dual-targeted capability in cells.•TSPy-B could effectively inhibit tumor growth and had good biological safety. Rational design of organelle targeted therapeutic platform in where the drug can be targeted to destroy tumor cells as much as possible, is one of the effective ways to improve the therapeutic outcomes and minimize the cytotoxicity to normal cells. Here, photosensitizer TSPy-B with aggregation-induced emission (AIE) feature, biotin receptor and mitochondria dual-targeted capability, and high reactive oxygen species (ROS) generation efficiency was designed for fluorescence imaging guided photodynamic therapy (PDT) by linking biotin group to D-π-A type AIE dyes via ester bonds. Notably, cell imaging experiments showed that TSPy-B could selectively target tumor cells with biotin receptor overexpression and further exhibit mitochondria targeting ability. The in vitro anticancer mechanism confirmed that after cell internalization, TSPy-B localized in the mitochondrial site and produced ROS resulting in mitochondrial dysfunction and cell death. ROS generation experiments showed that TSPy-B could simultaneously produce 1O2 and highly toxic free radicals which not depended on the oxygen level of solid tumor. The cell killing effect of TSPy-B was also confirmed in hypoxic culture model. In vivo photodynamic therapy experiments demonstrated that TSPy-B could effectively inhibit tumor growth and had good biological safety. This work provides a choice for development of highly targeted photosensitizers for clinical fluorescence imaging guided PDT.