Smart Probe for Tracing Cancer Therapy: Selective Cancer Cell Detection, Image-Guided Ablation, and Prediction of Therapeutic Response In Situ

Abstract

Integrated diagnosis and therapy systems that can offer traceable cancer therapy are in high demand for personalized medicine. Herein, a pH-responsive polymeric probe containing tetraphenylsilole (TPS) with aggregation-induced emission characteristics and pheophorbide A (PheA) photosensitizer (PS) with aggregation-caused quenching property for tracing the whole process of cancer therapy is reported. At physiological conditions (pH 7.4), the probe self-assembles into nanoparticles (NPs), which show weak fluorescence of PheA with low phototoxicity, but strong green fluorescence from TPS for probe self-tracking. Upon uptake by cancer cells and entrapment in lysosomes (pH 5.0), the NPs disassemble to yield weak emission of TPS but strong red fluorescence of PheA with restored phototoxicity for PS activation monitoring. Upon light irradiation, the generated reactive oxygen species can cause lysosomal disruption to trigger cell apoptosis. Meanwhile, the probe leaks to the cytoplasm (pH 7.2), where the TPS fluorescence is restored for in situ visualization of the therapeutic response. The probe design thus represents a novel strategy for traceable cancer therapy.