Targeted Drug Delivery Via Cell-Nanoparticle Hybridization for Enhanced Efficacy and Reduced Off-Target Toxicity

Statement of Purpose The immobilization of surface-modified polyamidoamine (PAMAM) dendrimers on the cell surface introduces a novel approach for efficient and specific cellular uptake of therapeutic-carrying nanoparticles. This cell surface-nanoparticle hybridization event takes place via bioorthogonal copper-free click chemistry between a dibenzocyclooctyne (DBCO) group conjugated onto the dendrimer and azide-capped glycans expressed on the cell membrane through metabolic incorporation of azido sugars. This particular cell-nanoparticle hybridization method can be exploited to efficiently and uniformly deliver a variety of therapeutic, genetic or fluorescent payloads directly into cells. In this study, this method was employed to deliver the anticancer drug Camptothecin (CPT) to reduce the minimum incubation time required for cancer cell death while reducing off-target effects