Gated Delivery of Veratridine by Nanoassemblies for Treatment of Colorectal Cancer

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Colorectal cancer (CRC) originates in the lining of the colon (large intestine) or rectum, which are the final portions of the large intestine, closest to the anus. It is the third most common non-skin cancer diagnosed in men and women in the U.S. The number of diagnoses of colorectal cancer developed gradually over many years. American cancer society identified it as the second highest cause of cancer deaths in the last few years. Unlike other cancer treatments, radiation therapy does not control and cure colon cancer cells. So, cancer care teams will administer their medications with chemotherapy to improve patients curing rate after the surgery. In chemotherapy, medicines will transfer through the whole body and will affect both cancer and healthy cells. Targeted medicinal treatment will attack specific cancer cells rather than attacking all cells, including healthy ones. Our research work actively focused on designing gated veratridine (VTD) drug delivery method by mesoporous silica nanoparticles (MCM-41 MSNs) to target colorectal cancer cells. MCM-41 MSNs sealed by an enzymatically cleavable protein will deliver selective VTD drug to the colon cancer cells. I have examined the potential of casein and Bovine Serum Albumin (BSA) proteins to seal the pores of the MCM-41 nanoparticles. Our preliminary data have shown that covalent attachment of BSA and casein to the silica nanoparticles by the amide and isocyanate chemistries slow down the release of the model drug eugenol from MSNs. Enzyme responsive studies have shown that the rate of release is substantially increased by the enzymatic cleavage of BSA and Casein, which proves the concept. We will improve this system by replacing the model eugenol with veratridine (VTD) and the model casein with metalloproteins before we send this developed drug delivery method to test for mouse models.

First Advisor

Grigoriy Sereda

Second Advisor

Khosrow Rezvani

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