使用金属无机纳米载体触发RNAi治疗。,Molecular Pharmaceutics

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使用金属无机纳米载体触发RNAi治疗。
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-06-25 , DOI: 10.1021/acs.molpharmaceut.9b00021
Eva Villar-Alvarez , Baltazar H Leal , Adriana Cambón , Alberto Pardo , Raquel Martínez-Gonzalez , Javier Fernández-Vega , Sonia Al-Qadi , Víctor X Mosquera ₁ , Alberto Bouzas ₁ , Silvia Barbosa , Pablo Taboada

Affiliation

小干扰RNA（siRNA）的给药是治疗遗传性疾病（例如阿尔茨海默氏病或某些类型的癌症）的一种非常有趣的治疗选择，但其有效传递仍然是一个挑战。在本文中，开发了具有聚电解质层功能的基于Au纳米棒（GNR）的平台，并将其分析为潜在的siRNA纳米载体。通过逐层组装技术，通过交替沉积带相反电荷的聚苯乙烯磺酸盐，PSS，聚赖氨酸，PLL和siRNA生物聚合物，将聚合物层成功地组装在颗粒表面上。透明质酸层是为了为纳米结构提供潜在的靶向能力以及在生理介质中的胶体稳定性。一旦获得了杂合纳米载体，货物就会释放出来，研究了它们在生理相关介质中的胶体稳定性，细胞毒性，细胞内在化和摄取以及敲低活性。本发明的杂合颗粒通过蛋白酶辅助的和/或光触发的释放机制在细胞内释放遗传物质，以便根据需要控制寡核苷酸的递送。另外，观察到杂合的纳米载体对细胞无毒并且可以有效地将遗传物质传递到细胞质中。本文提出的基于GNR的纳米载体可提供合适的环境，以加载和保护足够数量的遗传材料，从而使基因的有效且持续的敲除能够长时间（72小时内高达93％）表达，这是由于其缓慢降解所致。 PLL，未观察到不良的副作用。

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Triggered RNAi Therapy Using Metal Inorganic Nanovectors.

The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.

更新日期：2019-06-12

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