Lipid droplets-mediated delivery of curcumin for targeted mitochondrial photodynamic therapy

Curcumin (CUR) exhibits considerable potential for applications in photodynamic therapy (PDT). Nevertheless, its hydrophobic nature and low bioavailability necessitate the development of advanced delivery systems. Lipid droplets (LDs), intracellular organelles characterized by a phospholipid monolayer shell enclosing a neutral lipid core, serve as ideal reservoirs for lipid-soluble drugs. Notably, lipids stored in LDs can be transported to mitochondria through the β-oxidation metabolic pathway. In this study, we exploited LDs as drug carriers to encapsulate curcumin, constructing curcumin-loaded LDs (CUR-LDs) that capitalize on the intrinsic interplay between LDs and mitochondria to enable targeted mitochondrial drug delivery. In vitro PDT assays using CUR-LDs demonstrated a significant enhancement in intracellular reactive oxygen species (ROS) production, together with compromised mitochondrial function, reduced mitochondrial membrane potential, and apoptotic cell death. These findings not only provide experimental evidence to support the development of LDs as a novel mitochondria-targeted drug delivery system but also present an innovative curcumin formulation with promising utility for cancer therapy.