Amine as a bottom-line functionality on DDS surface for efficient endosomal escape and further subcellular targets

Abstract

Subcellular targeting of drug delivery system (DDS) and hence delivery of drugs to individual organelles enhance efficacy, efficiency and effectiveness of drug treatment, and subsequently trim adverse cytotoxic effects. But efficient subcellular targeting is often limited due to their endosomal trapping and lysosomal degradation. Here we report a pilot study using quantum dot (QD) based smart nanoparticle as model DDS of small hydrodynamic diameter that can escape endosome efficiently due to surface amine functionalities having weak basic properties on its surface and target to the cell nucleus. We have synthesized high quality QD using colloidal synthesis technique and introduced optimum ratio of primary, secondary and tertiary amines on their surface using surface decoration strategies, having high cellular uptake and efficient endosomal escape property and trafficked to cell nucleus after functionalization with TAT peptide. Our developed polymeric coating chemistry has been exploited for the extensive variation and finer adjustment of different amine functionalities on the DDS surface. Developed amine functionalization method is simple, versatile, adjustable for further functional variations and extendable to different DDS.