Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
Biomater Sci. 2017 Oct 24;5(11):2328-2336. doi: 10.1039/c7bm00729a.
In the present study, a pH sensitive nanogel platform for gene delivery was developed. The cationic nanogels based on dendritic polyglycerol (dPG) and low molecular weight polyethylenimine units were able to encapsulate siRNA during the manufacturing process. The thiol-Michael nanoprecipitation method, which operates under mild conditions and did not require any catalyst or surfactant, was used to develop tailor-made nanogels in the sub-100 nm range. The incorporation of pH sensitive benzacetal-bonds inside the nanogel network enables the controlled intracellular release of the cargo. The functionality to transport therapeutic biomolecules was tested by an in vitro GFP-siRNA transfection assay. Encapsulated siRNA could silence GFP expressing HeLa cells (up to 71% silencing in GFP). Furthermore, significantly reduced toxicity of the nanogel platform compared to the non-degradable PEI was observed. These properties realize a new carrier platform in the field of gene therapy.
在本研究中，开发了一种用于基因传递的 pH 敏感纳米凝胶平台。基于树枝状聚甘油(dPG)和低分子量聚乙烯亚胺单元的阳离子纳米凝胶能够在制造过程中包裹 siRNA。采用硫醇-Michael 纳米沉淀法，在温和条件下操作，无需任何催化剂或表面活性剂，可在亚 100nm 范围内开发定制的纳米凝胶。纳米凝胶网络中内的 pH 敏感苯乙缩醛键可实现货物的受控细胞内释放。通过体外 GFP-siRNA 转染实验测试了运输治疗性生物分子的功能。包裹的 siRNA 可以沉默表达 GFP 的 HeLa 细胞（GFP 沉默率高达 71%）。此外，与不可降解的 PEI 相比，观察到纳米凝胶平台的毒性显著降低。这些特性实现了基因治疗领域的新型载体平台。
