Biodegradable CCK-receptor targeted nanoparticle for the treatment of Cancer

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Categories:  “Cancer Therapeutics

Reference #: 2016-020

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)


Georgetown University investigators have developed targeted siRNA delivery system that selectively binds to cell surface receptors on tumor cells. The siRNA-polymer complex binds to a CCK ligand and allows for targeted delivery of siRNA into the cell. siRNA suppresses expression of cancer proteins that are responsible for tumor growth or metastasis. The nontoxic nanoparticle is designed to allow cellular entry of siRNA for specialized cancer treatment.

Pancreatic ductal Adenocarcinoma (PDAC) cells over-express the cholecystokinin-B(CCK-B) receptor and the re-expression of gastrin stimulates growth of the cancer by an autocrine mechanism through the CCK-B receptor. Down-regulation of GASTRIN mRNA by using RNAi inhibits cancer growth and metastasis. K-RAS expression is thought to bea driver of pancreatic cancer and down regulation of the same causes the carcinogenesis. The current delivery vehicle is designed to target both these genes and can safely bind to the cancer without off target toxicity.



Stage of Development

The nanoparticle is made up of a thiol-functionalized block polymer conjugated to a known CCK ligand and theconstruct is complexed with the specific siRNA, such as GASTRIN and K-RAS. In-vivo efficacy is proved inPancreatic Ductal Adenocarcinoma xenograft models. Pre-clinical animal studies show a significantly decrease insize of the tumors and lack of metastasis in mice treated with the targeted siRNA construct.

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