pH-Triggered release of gemcitabine from polymer coated nanodiamonds fabricated by RAFT polymerization and copper free click chemistry

Abstract

Prodrug (gemcitabine)-based polymer coated nanodiamonds (NDs) were fabricated by grafting onto method and strain-promoted alkyne–azide cycloaddition (SPAAC) click chemistry. The polymers were synthesized by polymerization of a gemcitabine prodrug monomer and oligoethylene glycol methyl ether acrylate (OEGMEA) using a dibenzocyclooctyne (DBCO) containing reversible addition-fragmentation transfer (RAFT) agent. The covalent conjugation between the polymers and surface groups was carried out through an efficient approach by copper free click chemistry. The resulting NDs were found to release the drug in its active form much faster in acidic environment than in physiological condition. The composition of the polymer shell and the coating modality significantly influence the IC₅₀ values of the obtained NDs for AsPC-1 cells. Specifically, with the NDs coated with copolymers containing higher OEGMEA content displaying comparable IC₅₀ as free gemcitabine, whereas NDs coated with lower fraction of OEGMEA result in higher IC₅₀ values.