Exploring the size of DNA functionalized gold nanoparticles for high efficiency exosome uptake and sensitive biosensing

Exosomes are nanoscale lipid vesicles that play important roles in oncogenesis and tumor heterogeneity. Recently, more attentions have been attracted for the analysis of exosomes by using AuNPs-based nanoprobes due to their unique physicochemical properties. In this regard, the geometrical parameters of AuNPs have high impact on the performance for exosome sensing, whereas the related mechanistic studies have not been reported so far. Herein in this work, we symmetrically explored the size influence of DNA functionalized AuNPs on their uptake efficiency by exosomes, and found that the uptake efficiency was highly size-dependent. Based on these interesting discoveries, we developed AuNPs-based nanoprobes for the in-situ detection of miRNA in exosomes. The nanoprobe prepared using 5 nm AuNPs exhibits the highest sensitivity with a detection limit of 6.53 x 10(3) particles/mu L, which is about 2 orders of magnitude lower than that of traditional 13 nm AuNPs. Furthermore, the nanoprobe based on 5 nm AuNPs was successfully used in clinical serum samples to differentiate cancer patients from healthy individuals. All these results advise that DNA-AuNPs can be easily tailored through size modulation to design functional nanoprobe with excellent exosome uptake properties and improved performance in exosome sensing applications.