Biomineralization of Aggregation-Induced Emission-Active Photosensitizers for pH-Mediated Tumor Imaging and Photodynamic Therapy

As an efficient, noninvasive, and high spatiotemporal resolved approach, photodynamic therapy (PDT) has high therapeutic potential for cancer treatment, whereas its development still faces a number of challenges, such as the lack of efficient and stable photosensitizers (PSs) and the inadequate ability of PSs to accumulate at tumor sites and target responses. Herein, a pH-responsive calcium carbonate (CaCO3)-mineralized AIEgen nanoprobe was prepared by using bovine serum albumin as the skeleton and loaded with a mitochondria-specific aggregation-induced emission (AIE)-active PS of 1-methyl-4-(4-(1,2,2-triphenylvinyl)styryl)quinolinium iodide (TPE-Qu(+)), which exhibits superior singlet oxygen (O-1(2))-generation ability and meanwhile possesses a bright near-infrared fluorescence emission. The biomineralized nanoparticles have small sizes (100 +/- 10 nm) with good water dispersion and stability. With an increase in acidity (pH = 7.4-5.0), the internal TPE-Qu+ molecules are released gradually and accumulated in the mitochondria due to their hydrophobicity and electropositivity and then generate fluorescence emission and PDT under an external light source. Tumor inhibition and low acute toxicity were further successfully confirmed by the intracellular uptake test and 4T1-tumor-bearing mouse model.