Polymer-directed supramolecular assembly of photosensitizers: Evocation of photothermal effect and highly efficient loading of disulfiram for chemo-phototherapy of cancer

Abstract The photodynamic therapy (PDT) effect of photosensitizers (PSs) in cancer is limited by the short wavelength light and random aggregation of PSs. Devising a nanosystem with orderly assembled PSs for simultaneous photodynamic and photothermal therapy using longer wavelength light is attractive yet challenging. Herein, we reported polymer-directed J-aggregation of cationic PS, 5, 10, 15, 20–tetrakis(4-aminophenyl)porphyrin (TAPP), by using a negatively charged polymer. The as-prepared blank nanoparticles (NPs) and disulfiram-loaded NPs (PTD, with a high disulfiram loading content of 10%) showed strong absorption of near infrared light. PTD NPs had excellent photothermal effect and disulfiram-enhanced singlet oxygen generation in aqueous upon irradiation of 808 nm laser, a light source with longer wavelength than the intrinsic excitation wavelength of TAPP (660 nm) for PDT. In vivo antitumor study suggests that PTD plus 808 nm laser completely ablated 4T1 tumors in mice by photoacoustic imaging-guided chemo-phototherapy. Our work provides a strategy of devising PS-based nanotherapeutic system as robust drug carriers with fascinating optical properties for enhanced phototherapy.