Graphitic carbon nitride nanosheets as a multifunctional nanoplatform for photochemical internalization-enhanced photodynamic therapy

Abstract

Photodynamic therapy (PDT) has been widely used as a noninvasive and moderate technique in precision cancer therapy by destroying cancer cells via light-induced reactive oxygen species (ROS). However, the overproduction of heat shock protein 70 (HSP70) induced by ROS will contribute to the cell survival under harsh conditions, finally leading to decreased PDT efficiency. To overcome this issue, herein, for the first time, we have prepared an HSP70 inhibitor (2-phenylethynesulfonamide (PES))-loaded graphitic carbon nitride nanosheet (GCNS) as a multifunctional nanoplatform (GCNS-PES) for enhanced PDT. By taking advantage of commendable PDT efficiency, strong blue fluorescence, satisfactory drug loading capacity and good water dispersity, the GCNS can simultaneously serve as a photosensitizer, an imaging agent and a drug carrier. Moreover, when the nanoplatform is restricted in the endo/lysosome vesicles through endocytosis, the GCNS can generate ROS effectively under visible light irradiation to promote the lipid peroxidation of endo/lysosomal membranes and accelerate the liberation of GCNS and PES into the cytoplasm. Finally, the tolerance of cancer cells to ROS is decreased by PES-induced HSP70 inactivation, and therefore the efficiency of PDT is significantly enhanced. As a result, GCNS-PES can serve as a promising therapeutic nanoplatform for photo-controlled cancer therapy.