Engineered Polymer-siRNA Polyplexes Provide Effective Treatment of Lung Inflammation

被引：34

作者：

Jeon, Taewon ^{[1
,2
]}

Luther, David C. ^{[2
]}

Goswami, Ritabrita ^{[2
]}

Bell, Charlotte ^{[3
]}

Nagaraj, Harini ^{[2
]}

Cicek, Yagiz Anil ^{[2
]}

Huang, Rui ^{[2
]}

Mas-Rosario, Javier A. ^{[1
]}

Elia, James L.

Im, Jungkyun ^{[2
,4
]}

Lee, Yi-Wei ^{[2
]}

Liu, Yuanchang ^{[2
]}

Scaletti, Federica ^{[2
]}

Farkas, Michelle E. ^{[1
,2
]}

Mager, Jesse ^{[3
]}

Rotello, Vincent M. ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Mol & Cellular Biol Grad Program, Amherst, MA 01003 USA

[2] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA

[3] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA

[4] Soonchunhyang Univ, Dept Chem Engn, Asan 31538, South Korea

来源：

ACS NANO | 2023年 / 17卷 / 05期

关键词：

Anti-inflammatory; siRNA; polymer; polyplex; cytosolic delivery; lung inflammation; DIRECT CYTOSOLIC DELIVERY; MONOCLONAL-ANTIBODIES; NANOPARTICLES; EFFICIENT; DISEASE; PROGRESS; THERAPY; ASTHMA; FATE;

D O I：

10.1021/acsnano.2c08690

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Uncontrolled inflammation is responsible for acute and chronic diseases in the lung. Regulating expression of pro-inflammatory genes in pulmonary tissue using small interfering RNA (siRNA) is a promising approach to combatting respiratory diseases. However, siRNA therapeutics are generally hindered at the cellular level by endosomal entrapment of delivered cargo and at the organismal level by inefficient localization in pulmonary tissue. Here we report efficient anti-inflammatory activity in vitro and in vivo using polyplexes of siRNA and an engineered cationic polymer (PONI-Guan). PONI-Guan/siRNA polyplexes efficiently deliver siRNA cargo to the cytosol for highly efficient gene knockdown. Significantly, these polyplexes exhibit inherent targeting to inflamed lung tissue following intravenous administration in vivo. This strategy achieved effective (>70%) knockdown of gene expression in vitro and efficient (>80%) silencing of TNF-alpha expression in lipopolysaccharide (LPS)-challenged mice using a low (0.28 mg/kg) siRNA dosage.

引用

页码：4315 / 4326

页数：12

共 66 条

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