Orally delivered thioketal-nanoparticles loaded with TNFα-siRNA target inflammation and inhibit gene expression in the intestines

By D. S. Wilson, G. Dalmasso, Lixin Wang, S. Sitaraman, D. Merlin, N. Murthy. Nature Materials, 2010

661 citations recorded by the source corpus.

Gene silencing via orally delivered small interfering RNAs (siRNAs) represents a promising treatment strategy for numerous gastrointestinal (GI) diseases associated with chronic intestinal inflammation; however, the oral delivery of siRNA to inflamed isntestinal tissues remains a major challenge. Here, we present a delivery vehicle for siRNA, termed thioketal nanoparticles (TKNs), that can localize orally deliver siRNA to sites of intestinal inflammation, and thus inhibit gene expression in diseased intestinal tissue. TKNs are formulated from a new polymer, poly-(1,4-phenyleneacetone dimethylene thioketal) (PPADT), that degrades selectively in response to reactive oxygen species (ROS). Therefore, when delivered orally, TKNs release siRNA in response to the abnormally high levels of ROS specific to sites of intestinal inflammation1–3. Using a murine model of ulcerative colitis (UC), we demonstrate that orally administered TKNs loaded with siRNA against the proinflammatory cytokine tumor necrosis factor-alpha (TNFα) diminish TNFα messenger RNA (mRNA) levels in the colon and protect mice from UC.

Subfields: Cancer Research, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9c5cbf669c3344ce2fbcbce1fd7f9c9408e2f1c1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. J. Hanes
2. L. Ensign
3. M. Esteban

In Molecular Biology

1. L. Ensign
2. J. Hanes
3. M. Esteban

Citations in the corpus

• Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers (2011, background): “Wilson and coworkers loaded the 600 nm particles with TNF-α-siRNA to treat mice with dextran sulfate sodium (DSS) induced ulcerative colitis [84]; TNF-α is integral in the onset and persistence of intestinal inflammation.”
• Nanoparticles in tissue engineering: applications, challenges and prospects (2018, methodology): “6 In the biomedical field, nanoparticles have been used for controlled drug delivery, 7,8 imaging of specific sites, probing of DNA structures, 9–11 biomolecular sensing, gene delivery, photo-thermal ablation of cells 12 and, most recently, TE.”
• The Smart Drug Delivery System and Its Clinical Potential (2016, background): “Reproduced with permission from reference [35].”