» Articles » PMID: 30087933

Enhancing Gene-Knockdown Efficiency of Poly(-isopropylacrylamide) Nanogels

Overview
Journal ACS Omega
Specialty Chemistry
Date 2018 Aug 9
PMID 30087933
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Polo-like-kinase 1 (PLK1), which is a serine-threonine protein kinase overexpressed in cancer cells, is known to regulate tumor growth and have recently gathered attention as a target gene for RNA interference because of the poor bioavailability and nonspecificity of the available inhibitors. However, the lower transfection efficiency of siRNA and its poor stability in biological mileu necessitate the need of efficient siRNA delivery systems. Here, we report efficacious polymeric nanoparticles for the delivery of PLK1 siRNA in mammalian cancer cells. -Isopropylacrylamide (NIPAm) and -isopropylmethacrylamide--NIPAm nanogels were synthesized and modified using poly-ε-lysine. Furthermore, their ability to induce gene silencing was investigated by flow cytometry and real-time polymerase chain reaction, and the silencing efficiency observed was related to the polymer composition and its effect on the gene loading and protection ability and the endosomal escape capability. This study attempts to leverage the understanding of the cell-material interaction, thus, addressing the bottlenecks of siRNA delivery for enhancing the efficacy of the poly(-isopropylacrylamide)-based delivery vehicle.

Citing Articles

Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery.

Zhang H, Keskin D, de Haan-Visser W, Zu G, van Rijn P, Zuhorn I Pharmaceutics. 2021; 13(11).

PMID: 34834380 PMC: 8618000. DOI: 10.3390/pharmaceutics13111964.


Peptide conjugation enhances the cellular co-localization, but not endosomal escape, of modular poly(acrylamide-co-methacrylic acid) nanogels.

Clegg J, Sun J, Gu J, Venkataraman A, Peppas N J Control Release. 2020; 329:1162-1171.

PMID: 33127451 PMC: 7904656. DOI: 10.1016/j.jconrel.2020.10.045.

References
1.
Bu Y, Yang Z, Li Q, Song F . Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells. Oncology. 2008; 74(3-4):198-206. DOI: 10.1159/000151367. View

2.
Eckerdt F, Yuan J, Strebhardt K . Polo-like kinases and oncogenesis. Oncogene. 2005; 24(2):267-76. DOI: 10.1038/sj.onc.1208273. View

3.
Zhao C, Ju J, Gao W, Yu W, Gao Z, Li W . Downregulation of PLK1 by RNAi attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis and inhibiting angiogenesis. Neoplasma. 2015; 62(5):748-55. DOI: 10.4149/neo_2015_089. View

4.
Haupenthal J, Bihrer V, Korkusuz H, Kollmar O, Schmithals C, Kriener S . Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels. Neoplasia. 2012; 14(5):410-9. PMC: 3384428. DOI: 10.1596/neo.111366. View

5.
Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T . In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials. 2003; 24(7):1121-31. DOI: 10.1016/s0142-9612(02)00445-3. View