One of the primary challenges associated with nanoparticle-dependent biological applications is that endosomal entrapment in a physiological environment severely limits the desired targeting and functionality of the nanoconstructs. This study sought to overcome that challenge through a systematic approach of gold nanorod (GNR) functionalization: evaluating the influence of both aspect ratio and surface chemistry on targeted cellular internalization rates and preservation of particle integrity. Owing to their unique spectral properties and enhanced surface area, GNRs possess great potential for the advancement of nanobased delivery and imaging applications. However, their ability for efficient intracellular delivery while maintaining their specific physiochemical parameters has yet to be satisfactorily explored. This study identified that longer and positively charged GNRs demonstrated a higher degree of internalization compared to their shorter and negative counterparts. Notably, of the four surface chemistries explored, only tannic acid resulted in retention of GNR integrity following endocytosis into keratinocyte cells, due to the presence of a strong protein corona matrix that served to protect the particles.

Taken together, these results identify tannic acid functionalized GNRs as a potential candidate for future development in nanobased biomolecule delivery, bioimaging, and therapeutic applications.