Photoresponsive prodrug-based liposomes for controllable release of the anticancer drug chlorambucil

The on-demand delivery and release of chemotherapeutic drugs have attracted great attention, among which photoresponsive prodrug systems have shown specific advantages for effective cancer treatment due to their spatiotemporal control, non-invasive nature and easy operation. Unlike the traditional strategy of physical encapsulation of drugs in liposomes, we herein report a biomimetic and photoresponsive drug delivery system (DDS) based on a lipid prodrug liposomal formulation (LNC), which combines the features of the prodrug and nanomedicines, and can realize photocontrollable release of anticancer drugs. The lipid prodrug comprises three functional moieties: a single-arm phospholipid (Lyso PC), an o-nitrobenzyl alcohol (NB) and chlorambucil (CBL). Before irradiation, LNC formed liposomal assemblies in water with an average size of about 200 nm, and upon light irradiation, the efficient photocleavage reaction of NB facilitated the disintegration of liposomal assemblies and the release of drug CBL. Photolysis analysis showed that LNC exhibited accurate and controllable drug release in response to UV 365 nm irradiation. Cell viability assays showed that LNC liposomes demonstrated very low cytotoxicity in the dark and high cellular toxicity upon light irradiation, with toxicity even higher than free CBL. Our results suggest that our photoresponsive lipid prodrug represents a promising strategy to construct controlled DDS for cancer therapy.