title: Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.
abstract: Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1530 3rd Avenue South, Birmingham, AL 35294, USA.
authors.forename: Amanee D
authors.initials: AD
authors.lastname: Salaam
authors.forename: Patrick T J
authors.initials: PT
authors.lastname: Hwang
authors.forename: Aliza
authors.initials: A
authors.lastname: Poonawalla
authors.forename: Hadiyah N
authors.initials: HN
authors.lastname: Green
authors.forename: Ho-wook
authors.initials: HW
authors.lastname: Jun
authors.forename: Derrick
authors.initials: D
authors.lastname: Dean
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008297:Male; D058612:Nanodiamonds / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D058612:Nanodiamonds; D004317:Doxorubicin