Controlled pH Stability and Adjustable Cellular Uptake of Mixed-Charge Nanoparticles

Nanoparticles functionalized with mixed self-assembled monolayers (m-SAMs) comprising positively and negatively charged thiols are stable at both low and high pH but precipitate sharply at the pH where the charges on the particle are balanced (pHprec). By adjusting the proportion of the positively and negatively charged ligands in the m-SAM or changing particle size, pHprec can be varied flexibly between ∼4 and ∼7. In addition, changes in the SAMs’ composition and particles’ net charge translate into different degrees of cellular uptake. Remarkably, the presence of the positively charged thiols allows for the uptake of particles having net negative charge.