Incorporation of active DNA/cationic polymer polyplexes into hydrogel scaffolds.

Incorporation of active DNA/cationic polymer polyplexes into hydrogel scaffolds.
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DOI:
10.1016/j.biomaterials.2010.08.016
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发表时间:
2010-12
期刊:
影响因子:
14
通讯作者:
Segura, Tatiana
Segura, Tatiana
中科院分区:
工程技术1区
文献类型:
--
作者:
Lei, Yuguo;Huang, Suxian;Sharif-Kashani, Pooria;Chen, Yong;Kavehpour, Pirouz;Segura, Tatiana

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DNA和siRNA的有效和持续局部递送将增加基因治疗在组织再生和癌症治疗中的适用性。一种有希望的方法是使用水凝胶支架来封装核苷酸并将其以纳米颗粒的形式递送到疾病部位。然而,这种方法目前受到限制,由于在装载过程中严重的纳米颗粒聚集,不能将浓缩的和活性的基因递送纳米颗粒装载到水凝胶中。在这里,我们提出了一种方法来加载浓缩和未聚集的非病毒基因递送纳米颗粒,使用DNA/聚乙烯亚胺(PEI)聚合物作为一个例子,到中性聚乙二醇(PEG),带负电荷的透明质酸(HA)和蛋白质纤维蛋白水凝胶交联通过各种化学。包封的复合物在体外和体内都具有高活性。我们相信这一过程将大大推进水凝胶支架介导的非病毒基因递送在组织再生和癌症治疗中的应用。
The effective and sustained delivery of DNA and siRNAs locally would increase the applicability of gene therapy in tissue regeneration and cancer therapy. One promising approach is to use hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated and active gene delivery nanoparticles into the hydrogels due to the severe nanoparticle aggregation during the loading process. Here, we present a process to load concentrated and un-aggregated non-viral gene delivery nanoparticles, using DNA/polyethylene imine (PEI) polyplexes as an example, into neutral polyethylene glycol (PEG), negatively charged hyaluronic acid (HA) and protein fibrin hydrogels crosslinked through various chemistries. The encapsulated polyplexes are highly active both in vitro and in vivo. We believe this process will significantly advance the applications of hydrogel scaffold mediated non-viral gene delivery in tissue regeneration and cancer therapy.
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