Strategies in the design of gold nanoparticles for intracellular targeting: opportunities and challenges

With unique physicochemical properties, gold nanoparticles (Au NPs) have demonstrated their potential as drug carriers or therapeutic agents. Effective guidance of Au NPs into specific intracellular destinations becomes increasingly important as we strive to further improve the efficiency of drug delivery and modulate controllable cellular responses. In this review, we summarized recent advances in designing Au NPs with the capabilities of cellular penetration and internalization, endosomal escape, intracellular trafficking and subcellular localization via various approaches including physical injection, tuning the physiochemical parameters of Au NPs, and surface modification with targeting ligands. Strategies for delivering Au NPs to specific subcellular destinations including the nucleus, mitochondria, endoplasmic reticulum, lysosomes are also discussed. Moreover, current challenges associated with intracellular targeting of Au NPs are discussed with future perspectives proposed.