Redox-responsive polycation-functionalized cotton cellulose nanocrystals for effective cancer treatment

Carbon nanotubes have excellent penetrability and encapsulation efficiency in the fields of drug and gene delivery. Because of their excellent physicochemical properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be easily cleaved from CNCs. The gene condensation ability, reduction sensitivity, cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs were investigated in detail. The CNC-SS-PDs exhibited good transfection efficiencies and low cytotoxicities. The needlelike shape of CNCs had an important effect on enhancing transfection efficiency. The antitumor effect of CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that the functionalization of CNCs with redox-responsive polycations is an effective method for developing novel gene delivery systems.