Tuning the Loading and Release Properties of MicroRNA-Silencing Porous Silicon Nanoparticles by Using Chemically Diverse Peptide Nucleic Acid Payloads,ACS Biomaterials Science & Engineering

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Tuning the Loading and Release Properties of MicroRNA-Silencing Porous Silicon Nanoparticles by Using Chemically Diverse Peptide Nucleic Acid Payloads
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2021-09-01 , DOI: 10.1021/acsbiomaterials.1c00431
Martina Neri ₁ , Jinyoung Kang ₂ , Jonathan M Zuidema ₃ , Jessica Gasparello ₄ , Alessia Finotti ₄ , Roberto Gambari ₄ , Michael J Sailor ₅ , Alessandro Bertucci ₁ , Roberto Corradini ₁

Affiliation

Peptide nucleic acids (PNAs) are a class of artificial oligonucleotide mimics that have garnered much attention as precision biotherapeutics for their efficient hybridization properties and their exceptional biological and chemical stability. However, the poor cellular uptake of PNA is a limiting factor to its more extensive use in biomedicine; encapsulation in nanoparticle carriers has therefore emerged as a strategy for internalization and delivery of PNA in cells. In this study, we demonstrate that PNA can be readily loaded into porous silicon nanoparticles (pSiNPs) following a simple salt-based trapping procedure thus far employed only for negatively charged synthetic oligonucleotides. We show that the ease and versatility of PNA chemistry also allows for producing PNAs with different net charge, from positive to negative, and that the use of differently charged PNAs enables optimization of loading into pSiNPs. Differently charged PNA payloads determine different release kinetics and allow modulation of the temporal profile of the delivery process. In vitro silencing of a set of specific microRNAs using a pSiNP-PNA delivery platform demonstrates the potential for biomedical applications.

中文翻译：

通过使用化学多样化的肽核酸有效负载调整 MicroRNA 沉默多孔硅纳米粒子的加载和释放特性

肽核酸 (PNA) 是一类人工寡核苷酸模拟物，由于其高效的杂交特性及其卓越的生物和化学稳定性，作为精准生物治疗药物而备受关注。然而，PNA 的细胞摄取不足是其在生物医学中更广泛应用的限制因素；因此，封装在纳米颗粒载体中已成为 PNA 在细胞中内化和递送的策略。在这项研究中，我们证明了 PNA 可以很容易地加载到多孔硅纳米粒子 (pSiNPs) 中，遵循一个简单的基于盐的捕获程序，迄今为止仅用于带负电荷的合成寡核苷酸。我们表明，PNA 化学的易用性和多功能性还允许生产具有不同净电荷的 PNA，从正电荷到负电荷，并且使用带不同电荷的 PNA 可以优化加载到 pSiNP 中。带不同电荷的 PNA 有效载荷决定了不同的释放动力学，并允许调节传递过程的时间曲线。使用 pSiNP-PNA 递送平台对一组特定 microRNA 进行体外沉默展示了生物医学应用的潜力。

更新日期：2021-09-01

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