Carrier‐free nanodrugs for stemness inhibition‐enhanced photodynamic therapy

Cancer stem cell (CSC) has been considered a key driver of tumor growth, recurrence, and metastasis due to its self-renewal and tumor initiation capacities called stemness. Stemness is also responsible for the high resistance of CSC to current therapeutic strategies, including photodynamic therapy (PDT) and chemotherapy. In this study, a carrier-free nanodrug (designated as MKCe6 nanoparticle [NP]) self-assembled by photosensitizer chlorin e6 (Ce6) and stemness inhibitor MK-0752 was prepared for effective tumor repression. Stemness inhibition caused by MK-0752 could sensitize CSCs to PDT. Benefiting from the high drug-loading capacity and efficient cellular internalization, MKCe6 NPs exhibited good performance in PDT and stemness inhibition. In this way, effective tumor growth repression and tumorigenesis inhibition by MKCe6 NPs were observed both in vitro and in vivo. This self-delivery nanodrug for stemness inhibition-enhanced photodynamic therapy may provide new insights for clinical cancer therapy.