A two-photon excited O2-evolving nanocomposite for efficient photodynamic therapy against hypoxic tumor

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (II) complex (Ru(bpy)(3)(2+)) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O-2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C3N4) for the first time. While exposured to two-photon laser, Ru(bpy)(3)(2+) was activated to generate singlet oxygen (O-1(2)) and Fe-C3N4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy)(3)(2+) to Fe-C3N4, O-2 generation by Fe-C3N4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating O-1(2) generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.