Intracellular mechanistic insights into cRGD-modified Bi2Se3 nanofoams for enhanced photothermal therapy via exocytosis inhibition

The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of Bi 2 Se 3 nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking. Our findings reveal that the cRGD-coated Bi 2 Se 3 nanofoams are internalized through three distinct endocytosis pathways: Rab34-mediated macropinocytosis, caveolae-dependent, and clathrin-dependent endocytosis. These nanofoams then accumulate in lysosomes via autophagy. Furthermore, inhibiting exocytosis reduces the loss of these nanofoams from cancer cells, enhancing photothermal and chemotherapy effects. This exocytosis-inhibiting strategy demonstrates significant potential for cancer therapy, validated by successful in vitro and in vivo results.