Ozdemir Nalan, Tuncel Ali, Kang Myungchan, Denkbaş Emir Baki
Department of Chemsitry, Hacettepe University, Beytepe, Ankara, Turkey.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2804-10. doi: 10.1166/jnn.2006.463.
In this study, a new thermosensitive material was proposed as a carrier for gene delivery. The thermosensitive submicron particles were synthesized by the dispersion copolymerization of N-isopropylacylamide (NIPA) with a relatively new, cationic comonomer, N-3-dimethylaminopropylmethacrylamide (DMAPM) with higher ionization ability with respect to the commonly used cationic comonomers. To achieve particle sizes smaller than 1 microm, suitable for gene delivery, the total monomer concentration in the dispersion copolymerization was kept at a sufficiently low level. The size of poly(NIPA-co-DMAPM) particles was determined as 454 nm, by AFM in dry state. The poly(NIPA-co-DMAPM) particles showed both temperature and pH sensitivity in the aqueous media. The plasmid DNA adsorption onto the thermosensitive cationic particles was investigated at different temperatures and pHs. The adsorbed amount of plasmid DNA onto the particles was significantly increased by the introduction of cationic comonomer. The equilibrium plasmid DNA adsorptions up to 13 mg/g dry particles were achieved at physiological pH. Approximately 36% w/w of adsorbed plasmid could be desorbed from the cationic nanolatex. The results of biocompatibility studies performed with mouse fibroblast cells showed the suitability of thermosensitive cationic particles for intended application.
在本研究中，提出了一种新型热敏材料作为基因递送载体。通过N-异丙基丙烯酰胺（NIPA）与一种相对较新的阳离子共聚单体N-3-二甲基氨基丙基甲基丙烯酰胺（DMAPM）进行分散共聚合成了热敏亚微米颗粒，相对于常用的阳离子共聚单体，DMAPM具有更高的电离能力。为了获得小于1微米、适合基因递送的粒径，分散共聚中的总单体浓度保持在足够低的水平。通过原子力显微镜（AFM）在干燥状态下测定聚（NIPA-co-DMAPM）颗粒的尺寸为454纳米。聚（NIPA-co-DMAPM）颗粒在水性介质中表现出温度和pH敏感性。研究了在不同温度和pH下质粒DNA在热敏阳离子颗粒上的吸附情况。通过引入阳离子共聚单体，颗粒上质粒DNA的吸附量显著增加。在生理pH下，质粒DNA在颗粒上的平衡吸附量达到13 mg/g干颗粒。约36%（w/w）吸附的质粒可从阳离子纳米胶乳中解吸。对小鼠成纤维细胞进行的生物相容性研究结果表明热敏阳离子颗粒适用于预期应用。
