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

Photodynamic therapy (PDT) has attracted much attentionin recentyears due to its high selectivity; however, limited by the heterogeneityof a tumor oxygen environment, the hypoxic region of a tumor willbe significantly resistant to PDT. Herein, we report an oxygen level-responsivetransformable therapeutic nanomedicine consisting of a hypoxia-responsivemolecule (Cy-NO2), a radical generator (ADVN), and a pH-responsivepolymer. In the normoxic region, Cy-NO2 in the nanomedicineplays the role of photosensitizer under 808 nm laser irradiation torealize effective PDT, while in hypoxic intracellular conditions,the Cy-NO2 will be converted into a photothermal agent,which can induce the decomposition of ADVN through photothermal effectto generate toxic free radicals for thermodynamic therapy. Therefore,by identifying the environmental characteristics and transformingtreatment approaches, this nanomedicine can achieve good therapeuticeffects under both normoxic and hypoxic conditions. This work offersa promising strategy for overcoming oxygen heterogeneity to achievesmart cancer therapy.