Monocomponent Nanodots with Dichromatic Output Regulated\nby Synergistic Dual-Stimuli for Cervical Cancer Tissue Imaging and\nPhotodynamic Tumor Therapy

Inflammation\nexists in the microenvironment of most, if not virtually\nall, tumors, which greatly exacerbates the difficulty of cancer treatment.\nConsidering the superiority of activatable photosensitizers (PSs),\na novel strategy of ‘making friends with the enemy’\nfor tumor treatment was proposed. In this strategy, the “enemy”\nrefers to inflammatory cytokines and the tumor site is targeted by\ndetecting the enemy. Upon detection, a dichromatic fluorescence signal\nis released and the PS is activated specifically by the inflammatory\ncytokines. In this study, a multifunctional PS (TPE-PTZ-Py) was rationally\ndesigned, which can be activated specifically under the synergistic\naction of hypochlorous acid (HClO) (one kind of inflammatory cytokines)\nand acid (one typical marker of tumor), and output a ratiometric fluorescence\nsignal simultaneously. The sulfoxide analogue (TPE-PTZO-PyH) as the\nresponse product effectively produced ¹O₂ (1.8-fold\nhigher than that obtained with Rose Bengal) and showed high phototoxicity\n(IC₅₀ < 7.6 μM). More importantly, imaging analyses\nconfirmed that TPE-PTZ-Py could be activated in human cervical cancer\ntissue. To date, several phenothiazine (PTZ)-based fluorescent probes\nhave been developed for the selective sensing and imaging of HClO\nin subcellular organelles; however, this is the first phenothiazine-based\nnanodrug designed for the treatment of inflammation-associated tumors\nwith a few side effects.