Slita Anna, Egorova Anna, Casals Eudald, Kiselev Anton, Rosenholm Jessica M
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity, Artillerigatan 6A, FI 20520 Turku, Finland.
D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproductology, Mendeleevskaya line, 3, Saint Petersburg 199034, Russia.
Asian J Pharm Sci. 2018 Nov;13(6):592-599. doi: 10.1016/j.ajps.2018.01.006. Epub 2018 Feb 21.
Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.
如今，使用小干扰RNA（siRNA）分子的基因治疗被认为是一种很有前景的方法。对于成功的治疗而言，开发一种稳定可靠的siRNA载体至关重要。像介孔二氧化硅纳米颗粒（MSN）这样的非病毒和非有机载体不存在大多数病毒载体的缺点，如毒性、免疫原性，但通常核酸承载能力较低。为克服这一障碍，我们在此用表面超支化聚合的聚乙烯亚胺（hbPEI）修饰了MSN的孔壁，hbPEI通过静电吸附提供了大量氨基以负载更多的siRNA分子。负载后，颗粒用第二层预聚合的PEI覆盖，以更好地保护孔内的siRNA，实现更有效的细胞摄取和内体逃逸。为测试PEI包被的siRNA/MSN的转染效率，使用了稳定表达绿色荧光蛋白（GFP）的MDA-MB 231乳腺癌细胞。我们证明，与未修饰的MSN相比，PEI包被的siRNA/MSN复合物能更有效地递送siRNA。因此，可以得出结论，经过适当表面修饰的MSN可被视为治疗性siRNA递送的潜在载体。
