Optimization of the kinetics of siRNA desorption from the surface of silicon nanoparticles

Melnikova Anzhelika, Kirkin Roman, Komarova Luidmila
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引用次数: 0

Abstract

Oncological diseases are one of the most significant medical and social diseases in most countries of the world. Over the past decades, the search and development of new drugs, treatment regimens and methods of molecular diagnostics of malignant neoplasms remains relevant. In turn, an important goal of molecular genetic research is to suppress the expression of genes responsible for the development of tumors. The key targets taken into account in the development of antitumor drugs are proteins involved in carcinogenic changes in the cell. One of the promising molecular targets for the development of medicinal compounds in targeted therapy of tumor diseases is poly(ADP-ribose)polymerase 1 (PARP1). A potential way to inhibit PARP1 even at the stage of protein translation is RNA interference due to small interfering RNAs (siRNAs). For the penetration of siRNAs into the target cell, it is necessary to develop a method of their transportation controlled in space and time. An actual direction for solving this problem is the use of highly stable porous silicon-based nanoparticles. In the current study, in order to increase the functionality of nanoparticles, their surface was modified with various agents (functionalization), providing increased efficiency of drug loading and more uniform release.
纳米硅表面siRNA解吸动力学优化
肿瘤疾病是世界上大多数国家最重要的医学和社会疾病之一。在过去的几十年里,恶性肿瘤的新药物、治疗方案和分子诊断方法的研究和发展仍然具有重要意义。反过来,分子遗传学研究的一个重要目标是抑制负责肿瘤发展的基因的表达。在开发抗肿瘤药物时,考虑到的关键靶点是参与细胞致癌变化的蛋白质。多聚腺苷核糖(adp -核糖)聚合酶1 (PARP1)是开发靶向治疗肿瘤疾病药物化合物的一个有前景的分子靶点。即使在蛋白质翻译阶段抑制PARP1的潜在方法是由小干扰RNA (sirna)引起的RNA干扰。为了使sirna渗透到靶细胞中,有必要开发一种空间和时间控制的sirna运输方法。解决这个问题的一个实际方向是使用高度稳定的多孔硅基纳米颗粒。在本研究中,为了增加纳米颗粒的功能,在其表面使用了各种各样的修饰剂(功能化),从而提高了载药效率和更均匀的释放。
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