In situ self-assembly of near-infrared-emitting gold nanoparticles into body-clearable 1D nanostructures with rapid lysosome escape and fast cellular excretion

The integration of strong near-infrared (NIR) emission, rapid lysosome escape, fast cellular excretion, and efficient total body clearance is highly desired for nanoparticles (NPs) to achieve synergistic functions in both molecular imaging and delivery. Herein, using a well-designed cyclopeptide (CP) that can spontaneously assemble into controllable nanofibers as template, a facile strategy is reported for in situ self-assembly of NIR-emitting gold NPs (AuNPs) into ordered and well-controlled one-dimensional (1D) nanostructures (AuNPs@CP) with greatly enhanced NIR emission (~ 6 fold). Comparing with the unassembled AuNPs, the AuNPs@CP are observed to enter living cells through endocytosis, escape from lysosome rapidly, and excrete the cell fast, which shows high gene transfection efficiencies in construction of cell line with ~ 7.5-fold overexpression of p53 protein. Furthermore, the AuNPs@CP exhibit high in vivo diffusibility and total body clearance efficiency with minimized healthy organ retention, which are also demonstrated to be good nanovectors for plasmid complementary deoxyribonucleic acid 3.1 (pcDNA3.1)(+)-internal ribosome entry site (IRES)-green fluorescent protein (GFP)-p53 plasmid with efficient p53 gene over-expression in tumor site. This facile in situ strategy in fabricating highly luminescent 1D nanostructures provides a promising approach toward future translatable multifunctional nanostructures for delivering, tracking, and therapy.