In recent years, a limited number of targeted therapies for cancer have transitioned to the clinic. While they show improvements in mitigating the side effects, the potential in selective targeting of cancer cells has not been realized yet, mostly due to a lack of unique cancer targets.
We are developing a drug delivery system that targets a cancer-specific glucose-regulated protein (GRP78), one of the most promising cancer cell surface receptors. Here we present a carrier system that employs a heterotrimer collagen/cell penetrating hybrid peptide as the carrier for small molecule drugs. The hybrid peptides were designed such that (1) they cannot form homotrimers under physiological conditions, and (2) they can be internalized only in the folded conformation. We determined that with the attachment of the recognition peptide with the GIRLRG sequence, cell surface GRP78 was successfully targeted using the heterotrimer complex system. A two-step drug targeting method system can further be implemented to enhance the selectivity of the drug delivery. We hope that this research will eventually lead to future clinical therapies that will largely diminish the side effects of chemotherapy.
|Commitee:||Bhandari, Deepali, Schwans, Jason|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 82/6(E), Masters Abstracts International|
|Subjects:||Biochemistry, Cellular biology, Oncology, Pharmacology, Organic chemistry, Public health|
|Keywords:||Cell surface, Drug carriers, Hybrid peptides, Mitigating side effects, Cancer cells, Cancer targets, Glucose-related protein, Small molecule drugs, Drug targeting, Clinical therapies , Chemotherapy|
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