Structure Design And In Vitro Evaluation Of PDMAEMA Nanocarriers For Gene/drug Delivery

The multiformity in polymer structure and self-assemble methods provide great chances to design multifunctional gene/drug delivery system. This study focused on the most important issues of delivery systems: safety and efficiency. Here, functional modification and multi-assembly were used to construct the vectors to improve biocompability and gene transfection efficiency or therapy efficiency simultaneously.In this work, in order to reduce the toxicity and meanwhile maintain high transfection efficiency, a new zwitterionic copolymer, polycaprolactone-g-poly-(dimethylaminoethyl methyacrylate-co-sulfadiazine methacrylate)(PC-SDZ) with unique pH-sensitivity, was designed and prepared. The physiochemical properties of self-assembly nanoparticles(NPs) including size, zeta potential, proton buffer capability and hydrophobicity were characterized. The transfection efficiency, endosome escape, intracellar distribution and toxicity of PC-SDZ NPs/DNA were also evaluated. The results showed that the incorporation of sulfadiazine into poly(dimethylaminoethyl methacrylate)(PDMAEMA) chains successfully mediates the surface properties including compacter shell structure, lower density of positive charges, stronger proton buffer capability, and enhanced hydrophobicity, which lead to reduction in toxicity and enhancements in stability, cellular uptake, endosome escape and transfection efficiency for the PC-SDZ2 nanoparticles(NPs)/DNA complexes.Our previous work had certificated PCL-g-PDMAEMA NPs showed excellent delivery efficiency for DNA and siRNA,but poor ability in loading antitumor drug. In order to improve the co-delivery efficiency of gene and drug, in this work, DOX molecules were bonded on side chains of PDMAEMA by hydrazone bond to form PCL-g-P(DMAEMA-co-HEMA)-hyd-DOX(PCD) NPs. PCD NPs/DNA complex was prepared and coated by HA-g-mPEG(HgP) as the surface layer. To improve the biocompability and prolong circulation time, the size, zeta-potential, transfection efficiency, toxicity and co-delivery effect were evaluated. The result showed that the multi-functional carriers performed high biocompability, high inhibiting effect against tumor cell in vitro and the smart response behaviors of drug release.