A Transformable Nanomedicine for Smart Cancer Therapy by Identifying the Environmental Characteristics

Photodynamic therapy (PDT) has attracted much attention in recent years due to its high selectivity; however, limited by the heterogeneity of a tumor oxygen environment, the hypoxic region of a tumor will be significantly resistant to PDT. Herein, we report an oxygen level-responsive transformable therapeutic nanomedicine consisting of a hypoxia-responsive molecule (Cy-NO 2 ), a radical generator (ADVN), and a pH-responsive polymer. In the normoxic region, Cy-NO 2 in the nanomedicine plays the role of photosensitizer under 808 nm laser irradiation to realize effective PDT, while in hypoxic intracellular conditions, the Cy-NO 2 will be converted into a photothermal agent, which can induce the decomposition of ADVN through photothermal effect to generate toxic free radicals for thermodynamic therapy. Therefore, by identifying the environmental characteristics and transforming treatment approaches, this nanomedicine can achieve good therapeutic effects under both normoxic and hypoxic conditions. This work offers a promising strategy for overcoming oxygen heterogeneity to achieve smart cancer therapy.