We report the synthesis of biodegradable hydrogel nanoparticles using a RAFT inverse miniemulsion cross-linking polymerization process with 2-(dimethylamino)ethyl methacrylate (DMAEMA) as monomer. The experimental conditions were optimized to yield a colloidally stable miniemulsion polymerization, which required protonation of DMAEMA using aqueous hydrogen chloride to ensure minimal partitioning to the continuous phase (cyclohexane). The nanoparticles were cross-linked using a disulfide cross-linker, thereby enabling subsequent degradation of the polymer network to its constituent primary chains by exposure to a reductive environment. The molecular weight distributions of the constituent primary chains were consistent with satisfactory control/livingness during the polymerization. These biodegradable hydrogel nanoparticles may have potential application as nanocarriers for encapsulation and controlled release of siRNA.