One-step approach of dual-responsive prodrug nanogels via Diels-Alder reaction for drug delivery

A novel strategy for the preparation of dual-responsive prodrug nanogels was proposed by Diels-Alder reaction. Firstly, poly(styrene- alt -maleic anhydride) copolymers were functionalized with furfuryl amine and hydrazine in a simple one-pot reaction. Secondly, doxorubicin (DOX) was further incorporated to copolymer via hydrazone linkage in the presence of dithiobismaleimidoethane as a cross-linking agent resulted in prodrug nanogels. The prodrug nanogels were stable under physiological condition while the disintegration of nanogels was taken place and DOX released rapidly in the redox medium. The prodrug nanogels presented strong toxicity towards HepG2 cell line, whereas they had almost no inhibition in HEK293 normal cell line. The results suggest that DOX conjugate-based nanogels would be a potential candidate for efficient drug nanocarrier. Graphical abstract