Stabilizing lysosome to facilitate verteporfin-based anticancer photodynamic therapy via trehalose co-assembled...

Trehalose (Tr) is a naturally occurring disaccharide extensively used as a stabilizing and cryoprotective agent for protein and cell preservation. Owing to its unique bioactivities, Tr-based biomaterials have recently emerged as a promising class of functional materials for biomedical applications. In this work, we reveal that Tr can protect lysosomes from the damage caused by verteporfin (VP), a clinically used photosensitizer. Inspired by this finding, a Tr nanogel (NG) ionically crosslinked with ferric ion was designed for the enhanced photodynamic therapy (PDT) of VP using a murine 4T1 breast cancer model. The constructed Tr/VP NG demonstrates a hydrodynamic diameter of 157.1 ± 2.8 nm, effective cellular uptake and a light-induced reactive oxygen species (ROS) generation in cells. Compared with free VP, the Tr/VP NG exhibits a comparable phototoxicity but with relieved dark toxicity in vitro, which could be evidenced by a less lysosomal leakage in cells and a lower hemolytic activity. Moreover, the Tr/VP NG mediates an elongated tumor accumulation of VP and meanwhile significantly improves antitumor PDT efficacy in vivo. This Tr/VP NG highlights both the feasibility of lysosome protection to minimize undesired dark toxicity of VP and a facile approach for engineering Tr-based materials.