Combinatory photodynamic and chemotherapy have demonstrated superior performance in cancer ablation over singular therapeutics. However, photodynamic therapy (PDT) often exhibits suboptimal efficacy for deep-seated tumors, owing to the limited penetration depth of illumination light, while chemotherapy is generally accompanied by severe side effects. Therefore, it is imperative to develop a functional nanoplatform for combinatory PDT and chemotherapy, which could, for PDT, achieve enhanced light penetration and, for chemotherapy, realize reduced therapeutic threshold dosage and a controllable drug release profile (e.g., minimized release in blood circulation but bursting release in the tumor microenvironment). Herein, we demonstrate a therapeutic nanoplatform composed of poly(acrylic acid) (PAA)-modified silica-coated Nd3+-doped upconversion nanoparticles decorated with methylene blue (MB) and doxorubicin (DOX) in silica and a PAA layer, respectively. Notably, 808 nm light is used to excite upconversion nanoparticles and further trigger the photosensitization behavior of MB in PDT, while the quick acid response of the PAA layer in the tumor acid environment introduces DOX bursting for optimized chemotherapy with significantly decreased therapeutic threshold dosage and minimized side effects. Importantly, the anticancer efficiency of the nanoplatform in vitro and in vivo shows an IC50 and a tumor inhibition rate of 12.55 μg mL-1 and 89.81%, respectively. This study provides a strategy for combinatory cancer therapy.
Keywords: chemotherapy; combinatory therapy; pH responsive; photodynamic therapy; upconversion nanoparticles.