Single molecular nanomedicine with NIR light-initiated superoxide radical, singlet oxygen and thermal generation for hypoxia-overcoming cancer therapy

While photodynamic therapy (PDT) of cancer has attracted much recent attention, its general applications are limited by the shallow tissue penetration depth of short-wavelength photons and the low oxygen contents in typical solid tumors. Herein, we develop small molecule (BthB)-based nanoparticles (NPs) which not only generate heat for effective photothermal therapy (PTT), but also generate superoxide radicals (O₂^·–) for hypoxia-overcoming photodynamic therapy (PDT) upon irradiation with an 808 nm laser. To the best of our knowledge, there are few reports of organic PDT agents which can work in hypoxia upon irradiation with photons having wavelengths longer than 800 nm. With the merits of NIR-excitability for better penetration depth, the BthB NPs are demonstrated both in vitro and in vivo to be highly effective for cancer ablation.