Advisory Committee Chair
Derrick Dean
Advisory Committee Members
Dale Feldman
Manoj Mishra
Vinoy Thomas
Yogesh Vohra
Document Type
Dissertation
Date of Award
2014
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
Abstract
Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer. Current chemotherapy regimens are plagued with issues such as toxicity, low bioavailability, and lack of specificity. To combat these issues, the feasibility of using nanodiamond particles (ND) to enhance the therapeutic efficacy of doxorubicin and resveratrol was investigated. The enhancement of chemotherapy using NDs was evaluated with three unique approaches: (1) drug mediation, (2) combination therapy, and (3) targeted drug delivery. The ND mediated doxorubicin system achieved a 50% improvement in therapeutic efficacy with over 60% cell death. The ND resveratrol combination therapy improved the efficacy of resveratrol by 40%, enhancing its typically low bioavailability. To facilitate targeting and further enhance the efficacy of doxorubicin, NDs were conjugated with the Asp-Gly-Glu-Ala (DGEA) peptide, which interacts with integrins over-expressed in metastatic prostate cancers, α2ß1. The resulting ND-DGEA doxorubicin targeted drug delivery system produced a 4 fold increase in efficacy with low drug doses. The findings from each component of the work confirmed that NDs are capable of enhancing therapeutic efficacy. The results from these studies are promising as they suggest that drug delivery with NDs provides a novel approach for decreasing toxicity and drug doses of traditional chemotherapy.
Recommended Citation
Salaam, Amanee, "Nanodiamond mediated therapies for prostate cancer" (2014). All ETDs from UAB. 2884.
https://digitalcommons.library.uab.edu/etd-collection/2884