蠕虫状聚离子复合型胶束的合成、组装和胶体稳定性

采用开环聚合方法制备了嵌段共聚物聚乙二醇-聚乙烯亚胺(PEG-b-PEI), 通过静电组装方法使其与质粒DNA(pDNA)在溶液中自发构筑成蠕虫状聚离子复合型胶束(PICmicelle), 利用原子力显微镜、 动态光散射、 Zeta电势和凝胶电泳等方法研究了血液或细胞间质中各种因素对胶束稳定性的影响. 结果表明, 在蠕虫状聚离子复合型胶束中, PEI和pDNA通过静电吸引构成疏水性内核, 而亲水性的PEG分子作为保护型外壳包裹在内核的表面. 在保持PEG链段长度不变的前提下, 增加PEI链段长度可明显增强PEI与pDNA的静电结合力, 有效地防止了NaCl对胶体结构的破坏, 而且有助于抑制阴离子的取代. 但增加PEI链段长度会导致胶束表面PEG分子含量的降低, 不利于胶束抵抗蛋白质的吸附和DNA酶的降解. 因此合理地调整PEG-b-PEI分子的结构, 对于获得高效、 安全和稳定的蠕虫状聚离子胶束具有重要意义.

Synthesis,Self-assembly and Colloidal Stability in Physiological Milieu of Worm-like PICmicelles of Poly(ethylene glycol)-b-poly(ethylenimine)/plasmid DNA

The block copolymers of poly(ethylene glycol)-b-poly(ethylenimine)(PEG-b-PEI) with different molecular ratios between PEG and PEI were synthesized by classical ring-opening polymerization.By simply mixing PEG-b-PEI with plasmid DNA(pDNA),worm-like polyion complex micelles(PICmicelles) were spontaneously formed in solution.Their structures and morphologies in physiological milieu were investigated and characterized by 1H NMR,gel permeation chromatography(GPC),dynamic light scattering(DLS),atomic force microscope(AFM) and gel electrophoresis,etc.The influence of numerous parameters,including NaCl dissociation,protein absorption,anionic species substitution and enzymatic digestion,on the colloidal stabilities of such worm-like PICmicelles were evaluated and demonstrated.The results indicated that the longer cationic segment could be helpful to efficiently condense pDNA and improve the colloidal stability against salt dissociation and anionic species substitution.However,it could also result in insufficient PEG shielding effect against protein absorption and enzymatic digestion.