To reduce premature drug release while ensuring burst intracellular drug release of solid lipid nanoparticle-based drug delivery system with clathrin modification.

Nanoscale drug delivery system (NDDS) with slow premature drug release (PDR) while ensuring burst intracellular drug release (BIDR) is becoming a hot point in NDDS-based nanomedicine. Here we used clathrin to modify a solid lipid nanoparticle (SLN)-based NDDS of salinomycin (SLN-SAL) to prepare NDDS with reduced PDR while ensuring BIDR. Drug-release-kinetic experiments revealed that clathrin modified SLN-SAL (CMSLN-SAL) reduced PDR while ensured BIDR of its prototype NDDS, SLN-SAL. Mechanism experiments revealed that clathrin modification reduced PDR of SLN-SAL through increasing the mechanical strength of SLN-SAL and ensured BIDR of SLN-SAL through lipid membrane fusion after its clathrin shell was de-polymerized by a cytoplasm enzyme, HSC70. In addition, CMSLN-SAL had significantly higher intracellular uptake and stronger inhibitive effects on cancer cells than that of SLN-SAL. These results demonstrated that clathrin modification is an effective way to reduce PDR while ensuring BIDR and increasing the anticancer effects of SLN-based NDDS.