title: New low molecular weight polycation-based nanoparticles for effective codelivery of pDNA and drug.
abstract: The development of new cationic nanoparticles that are safe and effective for biomedical applications has attracted considerable attention. Low molecular weight polycations generally exhibit low toxicity; however, their poor efficiency in drug delivery systems hampers their application. In this work, a series of new low molecular weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective codelivery of a gene and a drug. The BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in an aqueous solution. They could effectively bind pDNA with an appropriate particle size and ζ-potential. More importantly, the BIP-PGEA NPs demonstrated much higher transfection efficiencies than linear PGEA (L-PGEA) and the traditional "gold-standard" branched polyethylenimine (25 kDa). Moreover, the BIP-PGEA NPs could effectively entrap a hydrophobic anticancer drug such as 10-hydroxy camptothecin (CPT). The synergistic antitumor effect of the BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system, which contained cytosine deaminase and 5-fluorocytosine (CD/5-FC). The present strategy for preparing well-defined cationic nanoparticles from low-molecular-weight polycations could provide an intriguing method to produce new multifunctional, therapeutic NPs.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bingran
authors.initials: B
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhao
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D002166:Camptothecin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin; D004247:DNA; D049452:Green Fluorescent Proteins; D011073:Polyamines; D000071228:Polyelectrolytes; D011109:Polymethacrylic Acids; D011725:Pyridines; C485184:enhanced green fluorescent protein; C042535:polyglycidyl methacrylate; C023666:pyridine
keywords: ATRP; amphiphilic polymers; delivery; gene vector; nanoparticles