(8e) Enhanced Intracellular Concentration and Endosomal Release of Gold Nanorods Through Tannic Acid Functionalization: Implications for Advancement in Nano-Based Drug Delivery Mechanisms

Due to their unique properties, including a general biocompatibility, enhanced surface area, and a strong plasmonic response, gold nanorods (GNRs) have shown tremendous potential for applications including bio-imaging and drug delivery.  However, one primary challenge associated with nanoparticle-dependent delivery systems is the frequent occurs of endosomal entrapment; which severely limits the desired targetability and functionality of nano-constructs.  This study sought to overcome that challenge through a systematic approach to GNR functionalization for targeted cellular internalization and delivery potential, evaluating the influence of both aspect ratio and surface properties.  We identified that longer and positively charged GNRs demonstrated a higher rate of cellular internalization compared to their shorter and negatively charged counterparts.  Most interestingly, tannic acid (TA) functionalized GNRs were taken up independently of endocytosis, as assessed through the application of multiple endocytosis inhibitors.  This distinct manner of internalization resulted in a unique orientation of TA GNRs within the cells, as viewed through TEM.  To verify this phenomenon, GNRs were further functionalized with the fluorescent drug Doxorubicin and through confocal imaging the successful cytosolic delivery of the GNRs was ascertained, but only in conjunction with TA surface chemistry.  Taken together, these results identify TA functionalized GNRs as a strong candidate for future development of nano-based application in the areas of delivery mechanism and therapeutics.