Efficient poly(N-3-hydroxypropyl)aspartamide-based carriers via ATRP for gene delivery.

High-molecular-weight comb-shaped cationic copolymers have been of interest and importance as nonviral gene delivery carriers. Poly(DL-aspartamide)-based biomaterials with good degradability and excellent biocompatibility could be used as the potential backbones of gene vectors. In this work, atom transfer radical polymerization (ATRP) was proposed to prepare the biocleavable and biodegradable comb-shaped poly(N-3-hydroxypropyl)aspartamide (PHPA)-based gene carriers. The bioreducible ATRP initiation sites were first introduced onto PHPA backbones. Then, the well-defined comb-shaped vectors (SS-PHPDs) consisting of degradable PHPD backbones and disulfide-linked cationic P(DMAEMA) side chains were produced for gene delivery. The P(DMAEMA) side chains were readily cleavable from the backbones under reducible conditions. The degradability of PHPA backbones would benefit the final removal of the gene carriers from the body.