1 research outputs found
Well-Defined Cationic <i>N</i>鈥慬3-(Dimethylamino)propyl]methacrylamide Hydrochloride-Based (Co)polymers for siRNA Delivery
Cationic
glycopolymers have shown to be excellent candidates for
the fabrication of gene delivery devices due to their ability to electrostatically
interact with negatively charged nucleic acids and the carbohydrate
residues ensure enhanced stability and low toxicity of the polyplexes.
The ability to engineer the polymers for optimized compositions, molecular
weights, and architectures is critical in the design of effective
gene delivery vehicles. Therefore, in this study, the aqueous reversible
addition鈥揻ragmentation chain transfer polymerization (RAFT)
was used to synthesize well-defined cationic glycopolymers with various
cationic segments. For the preparation of cationic parts, <i>N</i>-[3-(dimethylamino)颅propyl]颅methacrylamide hydrochloride
(DMAPMA路HCl), water-soluble methacrylamide monomer containing
tertiary amine, was polymerized to produce DMAPMA路HCl homopolymer,
which was then used as macroCTA in the block copolymerization with
two other methacrylamide monomers containing different pendant groups,
namely, 2-aminoethyl methacrylamide hydrochloride (AEMA) (with primary
amine) and <i>N</i>-(3-aminopropyl) morpholine methacrylamide
(MPMA) (with morpholine ring). In addition, statistical copolymers
of DMAPMA.HCl with either AEMA or MPMA were also synthesized. All
resulting cationic polymers were utilized as macroCTA for the RAFT
copolymerization with 2-lactobionamidoethyl methacrylamide (LAEMA),
which consists of the pendent galactose residues to achieve DMAPMA路HCl-based
glycopolymers. From the in vitro cytotoxicity study, the cationic
glycopolymers showed better cell viabilities than the corresponding
cationic homopolymers. Furthermore, complexation of the cationic polymers
with siRNA, cellular uptake of the resulting polyplexes, and gene
knockdown efficiencies were evaluated. All cationic polymers/glycopolymers
demonstrated good complexation ability with siRNA at low weight ratios.
Among these cationic polymer-siRNA polyplexes, the polyplexes prepared
from the two glycopolymers, P颅(DMAPMA<sub>65</sub>-<i>b</i>-LAEMA<sub>15</sub>) and P颅[(DMAPMA<sub>65</sub>-<i>b</i>-MPMA<sub>63</sub>)-<i>b</i>-LAEMA<sub>16</sub>], showed
outstanding results in the cellular uptake, high EGFR knockdown, and
low post-transfection toxicity, suggesting the great potential in
siRNA delivery of these novel glycopolymers