Quantification of optimizing cellular uptake and excretion of nanoparticles by aggregation and de-aggregation mediated size changes

Gold nanoclusters of around 1.7 nm diameter were encapsulated in a matrix of the biodegradable polymer poly-L-arginine (PLAG), leading to nanoparticles (NPs) of around 70 nm diameter. It was shown that in order to achieve the same amount of endocytosed Au after 24 h exposure of HeLa cells to the NPs, for the encapsulated nanoclusters around 3 times less Au needed to be added to the cells, minimizing the necessary exposure concentration. On the other hand, due to the degradability of the PLAG, the intracellular Au could be exocytosed by around 3.5 times faster than for non-degradable Au NPs of similar initial size. This study thus quantified the effect of size-variable NPs on endo- and exocytosis. Aggregation of small NPs to bigger NPs in biodegradable matrices allows for improved endocytosis. De-aggregation of endocytosed aggregated NPs upon degradation of the biodegradable matrix allows for improved exocytosis, which is an important prerequisite for NPs clearance from cells, avoiding long-term toxicity.