摘要
高分子材料已被广泛应用于基因递送等生物医学领域,但是其材料毒性以及低转染效率等问题制约了这些高分子材料的临床以及商业化应用。高分子基因载体的转染效率、细胞毒性等通常与载体的分子量、电荷密度(通常也用氮磷比描述)之间存在紧密关联[1]。比如,载体的分子量或电荷密度越高,转染效率越高,但细胞毒性也越大。如何制备兼具高效、低毒等特点的高分子基因载体是当前该领域亟待解决的问题。我们针对这一问题,通过氟化修饰[2-4]和超分子化学[5-6]两种方法,使得多种高分子载体在低氮磷比或低分子量条件下实现了高效、低毒的基因转染。我们的研究获得了多种结构新颖且具有很好的生物学功能的高分子材料,为树形高分子材料进入临床以及商业应用奠定了基础,研究中所揭示的树形高分子材料结构与功能之间的关系也为进一步设计和优化高分子生物材料提供了理论依据。
Polymers are widely used in gene therapy, however, serious cytotoxicity and relatively low transfection efficacy limit the clinical applications of these polymers. Generally, the transfection efficacy and cytotoxicity of a polymeric gene carrier are correlated with their molecular weight and charge density. For example, the polymers with higher molecular weight and positive charge density usually represent higher transfection efficacy but also higher toxicity on the transfected cells. How to prepare polymeric gene carriers with both high transfection efficacy and low toxicity remains the major challenge in this field. Here we proposed two novel strategies to develop high efficient and low cytotoxic gene vectors by fluorination and supramolecular chemistry approaches. We obtained novel and high efficient gene carriers based on these methods. The researches provide several promising methods to design efficient and safe gene vectors for clinical gene therapy, and reveal the structure-activity relationship of functionalized polymers in gene delivery.
引文
[1]Yang JP,Zhang Q,Chang H,Cheng YY.Chemical Reviews,2015,115(11),5274-5300.
[2]Wang MM,Liu HM,Li Lei,Cheng YY.Nature Communications,2014,5,3053.
[3]Liu HM,Wang Y,Wang MM,Xiao JR,Cheng YY.Biomaterials,2014,35,5407-5413.
[4]Wang MM,Cheng YY.Biomaterials?2014,35,6603-6613.
[5]Shao NM,Dai TJ,Liu Y,Cheng YY.Chem.Commun.,2015,51,9741-9743.
[6]Liu HM,Wang H,Yang WJ,Cheng YY.J.Am.Chem.Soc.?2012?134,17680-17687.
[7]Wang H,Wang YT,Wang Y,Li TF,Liu HM,Zhang Q,Cheng YY.Angew.Chem.Int.Ed.,2015,54,11647-11651
[8]Liu CY,Shao NM,Wang YT,Cheng YY.Advanced Healthcare Materials,2016,5,584.
