Encapsulation of hydrophilic cancer drugs in polymeric nanocapsules was achieved in a one-pot process via the inverse miniemulsion periphery RAFT polymerization (IMEPP) approach. The chosen guest molecule was gemcitabine hydrochloride, which is used as the first-line treatment of pancreatic cancer. The resulting nanocapsules were confirmed to be ∼200 nm, with excellent encapsulation (∼96%) and loading (∼12%) efficiency. Postpolymerization reaction was successfully conducted to create glyocopolymer nanocapsules without any impact on the loads as well as the nanocapsules size or morphology. The loaded nanocapsules were specifically designed to be responsive in a reductive environment. This was confirmed by the successful disintegration of the nanocapsules in the presence of glutathione. The gemcitabine-loaded nanocapsules were tested in vitro against pancreatic cancer cells (AsPC-1), with the results showing an enhancement in the cytotoxicity by two fold due to selective accumulation and release of the nanocapsules within the cells. The results demonstrated the versatility of IMEPP as a tool to synthesize functionalized, loaded-polymeric nanocapsules suitable for drug-delivery application.