Well-Controlled Cationic Water-Soluble Phospholipid Polymer−DNA Nanocomplexes for Gene Delivery

Abstract

The facile synthesis of biocompatible and nontoxic gene delivery vectors has been the focus of research in recent years due to the high potential in treating genetic diseases. 2-Methacryloxyethyl phosphorylcholine (MPC) copolymers were recently studied for their ability to produce nontoxic and biocompatible materials. The synthesis of well-defined and water-soluble MPC polymer based cationic vectors for gene delivery purposes was therefore attractive, due to the potential excellent biocompatibility of the resulting copolymers. Herein, cationic MPC copolymers of varying architectures (block versus random) were produced by the reversible addition--fragmentation chain transfer (RAFT) polymerization technique. The copolymers produced were evaluated for their gene delivery efficacy in the presence and absence of serum. It was found that copolymer architectures and molecular weights do affect their gene delivery efficacy. The statistical copolymers produced larger particles, and showed poor gene transfection efficiency as compared to the diblock copolymers. The diblock copolymers served as efficient gene delivery vectors, in both the presence and absence of serum in vitro. To the best of our knowledge, this is the first report where the effect of architecture of MPC based copolymer on gene delivery efficacy has been studied.

Application of Living Free Radical Polymerization for Nucleic Acid Delivery

“…23,30,40-42 In general, these copolymers, regardless of specific architecture and form of hydrophilic modification, show significantly decreased cytotoxicity and enhanced colloidal stability relative to their respective homopolymers. For example, MPC-AEMA and MPC-APMA copolymers showed low protein adsorption likely due to the zwitterionic MPC component.…”

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…In addition to the previous TE and KE biological studies, microscopic methods have been frequently used to visualize the level of % GFP expression inside the cells after MVCLs containing dendritic headgroups [72,121] or cyclen-based [120] lipids; (c) cationic polymers based on PEI and PAA derivatives [124,183], phospholipid-polymer [203], aminoacid-based [126,127,190], chitosan [204], PDMAEMA [133], dendrimers as PAMAM derivatives [132,201], others cationic polymer-type [107,164] or PEG-PPG-PEG/cyclodextrin polyrotaxanes [89]; and (d) polycations based on calixarenes [166,205] or cyclodextrins [106,136,142]. With respect to gene silencing/knockdown siRNA studies, micrographs and/or images have been reported for systems where the following gene vectors have been used: (a) MVCLs based on dendritic lipids [104]; and (b) cationic polymers based on dendrimers [199], diblock copolymers [105] or POEAA [144], last one in vivo studies.…”

Zwitterionic drug nanocarriers: A biomimetic strategy for drug delivery

“…The block copolymers and statistical copolymers of MPC and 2-aminoethyl methacrylamide hydrochloride (AEMA) were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The diblock copolymers showed better gene transfection efficiency as compared to the statistical copolymers [88]. PC modified PEI with different grafting levels were designed which can form polyplexes with DNA.…”