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Effect of Confinement in Nanopores on RNA Interactions with Functionalized Mesoporous Silica Nanoparticles.
The Journal of Physical Chemistry B ( IF 3.3 ) Pub Date : 2020-09-03 , DOI: 10.1021/acs.jpcb.0c06536
M Arif Khan 1 , Maelyn R Kiser 1 , Mahsa Moradipour 1 , Emily A Nadeau 2 , Ramy W Ghanim 1 , Bruce A Webb 2 , Stephen E Rankin 1 , Barbara L Knutson 1
Affiliation  

Amine-functionalized mesoporous silica nanoparticles (MSNPAs) are ideal carriers for oligonucleotides for gene delivery and RNA interference. This investigation examines the thermodynamic driving force of interactions of double-stranded (ds) RNA with MSNPAs as a function of RNA length (84 and 282 base pair) and particle pore diameter (nonporous, 2.7, 4.3, and 8.1 nm) using isothermal titration calorimetry, extending knowledge of solution-based nucleic acid–polycation interactions to RNA confined in nanopores. Adsorption of RNA follows a two-step process: endothermic interactions driven by entropic contribution from counterion (and water) release and an exothermic regime dominated by short-range interactions within the pores. Evidence of hindered pore loading of the longer RNA and pore size-dependent confinement of RNA in the MSPAs is provided from the relative contributions of the endothermic and exothermic regimes. Reduction of endothermic and exothermic enthalpies in both regimes in the presence of salt for both lengths of RNA indicates the significant contribution of short-range electrostatic interactions, whereas ΔH and ΔG values are consistent with conformation changes and desolvation of nucleic acids upon binding with polycations. Knowledge of the interactions between RNA and functionalized porous nanoparticles will aid in porous nanocarrier design suitable for functional RNA delivery.

中文翻译:

限制在纳米孔中对功能化介孔二氧化硅纳米粒子与RNA相互作用的影响。

胺官能化的介孔二氧化硅纳米颗粒(MSNPA)是寡核苷酸用于基因传递和RNA干扰的理想载体。这项研究使用等温滴定法检查了双链(ds)RNA与MSNPA相互作用的热力学驱动力随RNA长度(84和282个碱基对)和颗粒孔径(无孔,2.7、4.3和8.1 nm)的变化量热法,将基于溶液的核酸-聚阳离子相互作用的知识扩展到纳米孔内的RNA。RNA的吸附过程分为两个步骤:由抗衡离子(和水)释放产生的熵促成的吸热相互作用和由孔内短程相互作用主导的放热机制。从吸热和放热方案的相对贡献中,可以看出MSPA中较长RNA受阻的孔隙加载和RNA的孔径依赖性限制。在盐存在下,两种长度的RNA在两种情况下吸热和放热焓的降低都表明短程静电相互作用的显着贡献,而ΔHΔG值与核酸与聚阳离子结合后的构象变化和去溶剂化相一致。RNA和功能化多孔纳米颗粒之间相互作用的知识将有助于设计适合功能性RNA输送的多孔纳米载体。
更新日期:2020-10-02
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