A family of hierarchically self-assembling linear-dendritic hybrid polymers for highly efficient targeted gene delivery.
A family of hierarchically self-assembling linear-dendritic hybrid polymers for highly efficient targeted gene delivery.
复制标题
DOI：
10.1002/anie.200502152
复制
发表时间：
2005-10
影响因子：
--
通讯作者：
Kris C Wood;S. Little;R. Langer;P. Hammond
中科院分区：
文献类型：
--
作者：
Kris C Wood;S. Little;R. Langer;P. Hammond
理想情况下，这样的系统是无毒的，非免疫原性的，并且由多功能的构建模块组成，允许最佳地递送到大量的细胞或感兴趣的组织。在此，我们首次提出了分层结构的线性-树枝状混合聚合物的设计、合成和评价，该混合聚合物与DNA自组装形成具有同心的、功能性“壳“的稳定纳米颗粒，该纳米颗粒显示出有效靶向递送所必需的独立可调性质。所得到的配体功能化系统证明了受体介导的靶向细胞递送，具有稳健的血清稳定性，转染效率超过了有效的市售聚合物聚（乙烯亚胺）（PEI）和低毒性，浓度比PEI所能抑制的浓度高两个数量级。这些系统可能在基于DNA或RNA的体内基因治疗系统中发现潜在的用途。基于基因的治疗的成功取决于在需要的时候和在需要的地方递送表达关键蛋白的基因的能力。迄今为止，还没有这样的治疗被批准用于临床应用，这主要是因为缺乏通用的、安全的、高效的基因传递系统。
Ideally, suchsystemswillbenontoxic,nonimmunogenic,andmadefromversatile building blocks that allow optimal delivery to arangeofcellsortissuesofinterest.Herein,forthefirsttime,wepresentthedesign,synthesis,andevaluationofauniquefamily of hierarchically structured linear-dendritic hybridpolymersthatself-assemblewithDNAtoformstablenano-particleswithaseriesofconcentric,functional“shells”thatdisplay independently tuneable properties necessary foreffective targeted delivery. The resultant ligand-functional-ized systems demonstrate receptor-mediated delivery totargeted cells with robust serum stability, transfection effi-cienciesthatexceedthemostefficientcommerciallyavailablepolymerpoly(ethylenimine)(PEI),andlowtoxicityatcon-centrationsonetotwoordersofmagnitudehigherthanthoseatwhichPEIistoxic.ThesesystemsmayfindpotentialutilityastargetedinvivogenedeliverysystemsforDNA-orRNA-basedtherapies.Thesuccess ofgene-basedtherapiesis dependentupontheabilitytodelivergenesthatexpresskeyproteinswhenandwheretheyareneeded.Asofyet,nosuchtherapieshavebeenapproved for clinical use, primarily because of the lackofversatile,safe,andefficientgenedeliverysystems.