Hydroxyl-rich branched polycations for nucleic acid delivery

Recently, nucleic acid delivery has become an amazing route for the treatment of various malignant diseases, and polycationic vectors are attracting more and more attention among gene vectors. However, conventional polycationic vectors still face many obstacles in nucleic acid delivery, such as significant cytotoxicity, high protein absorption behavior, and unsatisfactory blood compatibility caused by a high positive charge density. To solve these problems, the fabrication of hydroxyl-rich branched polycationic vectors has been proposed. For the synthesis of hydroxyl-rich branched polycations, a one-pot method is considered as the preferred method due to its simple preparation process. In this review, typical one-pot methods for fabricating hydroxyl-rich polycations are presented. In particular, amine-epoxide ring-opening polymerization as a novel approach is mainly introduced. In addition, various therapeutic scenarios of hydroxyl-rich branched polycations via one-pot fabrication are also generalized. We believe that this review will motivate the optimized design of hydroxyl-rich branched polycations for potential nucleic acid delivery and their bio-applications.