Ultrasmall Poly-L-Lysine Nanoparticles

The synthesis of ultrasmall poly-L-lysine (PLL) nanoparticles remains challenging using conventional nanogel preparation methods. This study investigates how the conformation of PLL precursor chains influences the resulting nanoparticle microstructure when crosslinking is performed under dilute conditions. Structural characterization by small-angle neutron scattering (SANS), complemented by dynamic light scattering (DLS) and proton nuclear magnetic resonance ($^1$H-NMR), reveals that pre-collapsing the precursor chains—achieved by adding salt or ethanol—and controlling the crosslinking density significantly affects nanoparticle size and compactness. Crosslinking in saline buffer with higher ionic strength results in smaller nanoparticles. In contrast, crosslinking in ethanol buffer solutions does not show structural changes during the reaction; however, upon buffer exchange, the nanoparticles adopt a similarly compact conformation as those prepared in saline buffer.