Dibenzothiophene-S,S-dioxide-Based Conjugated Polymers: All-in-One Two-Photon Fluorophore with ClO^– Degradation for Photodynamic Anticancer Therapy

Abstract

Photosensitizers (PSs) can be activated by light irradiation to yield reactive oxygen species (ROS) and elicit tumor cell death in photodynamic therapy (PDT). Nonetheless, well-suited multifunctional PSs anchoring with excellent two-photon absorption (2PA) and biodegradable properties are scarce. In this contribution, the hypochlorite (ClO − )-sensitive thiophene unit is inserted into a donor−acceptor− donor-type chromophore containing dibenzothiophene-S,S-dioxide. Then, the resultant poly(9,9-dioctylfluorene) derivative (PTSO) renders intensified green emission with high-fluorescence quantum yield (QY) up to 77.8% and pronounced 2PA property (2PA cross-section of 8062.5 GM at 780 nm) as well as rapid and sensitive oxidative degradation behavior by ClO − (less than 2 min and a detection limit of 3.48 μM for its nanoparticles). Integrated PTSO NPs are successfully implemented for two-photon microscopy imaging of in vitro cells and in vivo tissues, exhibiting outstanding properties of biocompatibility, internalization, penetrating depth, and laser wavelength. Of particular interest, PTSO NPs can boost poisonous ROS generation with a 1 O 2 generation quantum yield of 50.6% by activating the photophysical intersystem crossing (ISC) channel in combination with white light (400−780 nm) at 50 mW cm −2 , effectively inhibiting tumor growth with ignorable side effects in the A549 tumor-bearing mouse model. After fulfilling their photodynamic assignment, PTSO NPs will be biodegraded by endogenous ClO − , thus becoming smaller in size and being excreted from the body to circumvent possible long-term toxicity. All these merits illustrate that polymer PTSO is a potentially versatile photosensitizer for bioimaging and photodynamic anticancer therapy.