期刊
ACS APPLIED BIO MATERIALS
卷 4, 期 12, 页码 8267-8276出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.1c00810
关键词
RNA delivery; nanocarriers; nanoporous silica; mobility; polynucleic acids
资金
- National Science Foundation [1238087]
- National Science Foundation Experimental Program to Stimulate Competitive Research (EPSCoR) Research Infrastructure Improvement Track I grant [1355438]
- Directorate For Engineering [1238087] Funding Source: National Science Foundation
- Div Of Industrial Innovation & Partnersh [1238087] Funding Source: National Science Foundation
This study investigates the impact of confinement on the mobility of dsRNA in silica nanopores of different sizes. The results show that pore size affects the loading and exchange capability of dsRNA, while surface mobility plays a crucial role in the movement of dsRNA.
Nanoparticle delivery of polynucleic acids traditionally relies on the modulation of surface interactions to achieve loading and release. This work investigates the additional role of confinement in mobility of dsRNA (84 and 282 base pair (bp) sequences of Spodoptera frugiperda) as a function of silica nanopore size (nonporous, 3.9, 8.0, and 11.3 nm). Amine-functionalized nanoporous silica microspheres (NPSMs, similar to 10 mu m) are used to directly visualize the loading and exchange of fluorescently labeled dsRNA. Porous particles are fully accessible to both lengths of dsRNA by passive diffusion, except for 282 bp dsRNA in 3.9 nm pores. The stiffness of dsRNA suggests that encapsulation occurs by threading into nanopores, which is inhibited when the ratio of dsRNA length to pore size is large. The mobility of dsRNA at the surface and in the core of NPSMs, as measured by fluorescence recovery after photobleaching, is similar. The mobility increases with pore size (from 0.0002 to 0.001 mu m(2)/s for 84 bp dsRNA in 3.9-11.3 nm pores) and decreases with the length of dsRNA. However, when the dsRNA is unable to load into the pores (on nonporous particles and for 282 bp dsRNA in 3.9 nm pores), surface mobility is not detectable. The pore structure appears to serve as a source to provide a mobile network of dsRNA at the particle surface. The importance of mobility is demonstrated by exchange experiments, where NPSMs saturated with mobile dsRNA can exchange dsRNA with the surrounding solution, while immobile dsRNA is not exchanged. These results indicate that nanoparticle synthesis techniques that provide pores large enough to take up polynucleic acids internally (and not simply on the external surface of the particle) can be harnessed to design polynucleic acid/nanoporous silica combinations for controlled mobility as a path forward toward effective nanocarriers.
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