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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.

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With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments--DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.

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