Synthesis of Biocompatible PEG-Based Star Polymers with Cationic and Degradable Core for siRNA Delivery

• Published in: Biomacromolecules 2011-10, Vol.12 (10), p.3478-3486
• Main Authors: Cho, Hong Y, Srinivasan, Abiraman, Hong, Joanna, Hsu, Eric, Liu, Shiguang, Shrivats, Arun, Kwak, Dan, Bohaty, Andrew K, Paik, Hyun-jong, Hollinger, Jeffrey O, Matyjaszewski, Krzysztof
• Format: Article
• Language: English
• Subjects: Animals; Applied sciences; Biocompatibility; Biocompatible Materials - analysis; Biocompatible Materials - chemical synthesis; Biocompatible Materials - pharmacology; Biological and medical sciences; Cations - chemistry; Cell Line; Cell Survival - drug effects; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - metabolism; Drug Carriers - analysis; Drug Carriers - chemical synthesis; Drug Carriers - pharmacology; Endocytosis; Exact sciences and technology; Flow Cytometry; General pharmacology; Glutathione - metabolism; Light; Medical sciences; Methacrylates - chemistry; Methacrylates - metabolism; Mice; Organic polymers; Osteoblasts - drug effects; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; RNA, Small Interfering - chemistry; RNA, Small Interfering - metabolism; Scattering, Radiation
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm2006455

Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical copolymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross-linker, SS) via an “arm-first” approach. The star polymers had a diameter ∼15 nm and were degraded under redox conditions by glutathione treatment into individual polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by dynamic light scattering. The star polymers were cultured with mouse calvarial preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine biocompatibility. Data suggest star polymers were biocompatible, with ≥80% cell viability after 48 h of incubation even at high concentration (800 μg/mL). Zeta potential values varied with N/P ratio confirming complexation with siRNA. Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed by confocal microscopy and flow cytometry after 24 h of incubation.