Redox-Responsive Disulfide Cross-Linked PLA–PEG Nanoparticles

We have developed a strategy for the preparation of redox-responsive PEG–PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly(lactide)s were prepared by ring-opening copolymerization of l-lactide and 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167–300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, an...