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Impact of Docetaxel Conjugated Nanodiamonds on Gene Expression of Prostate Cancer (PC3) Cells

机译:多西他赛偶联纳米金刚石对前列腺癌细胞(PC3)基因表达的影响

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Prostate cancer (PC) is the second leading cause of adult male death in the United States which is due to uncontrolled growth of the prostate gland cells provoking the development of malignant tumors that could lead to death. Docetaxel (Dox) drug is used to treat PC but it becomes toxic at high concentrations or builds resistance to cancer cells in patients. Possible treatments for PC suggested the use of drug loaded nanoparticles as therapeutics. In this study, nanodiamonds (ND's) were used as carriers to deliver Dox to PC cells. ND's were conjugated with Dox and Dox along with RGD peptide using EDC/NHS chemistry. ND's in PC3 cells were tracked using ND-fluorescein which showed ND's were located in the cell nucleus after 24 hours of incubation. Drug release assay showed 92.3% of drug release from NDs in 24 hr. Microculture Tetrazolium Assay (MTT) assay showed 75% PC3 cells viability at 50μg/mL with ND's after 48 hr incubation compared to 50% with drug conjugated NDs stating that it efficient in causing cancer cell death. Gene expression analysis was conducted on PC3 cells with ND's and conjugated ND's after 24 hr incubation. NDR showed upregulation in many genes of PC cells. The study showed NDs can be used for efficient drug delivery for PC3 cells.
机译:前列腺癌(PC)是美国成年男性死亡的第二大主要原因,这是由于前列腺腺细胞的不受控制的生长引起了可能导致死亡的恶性肿瘤的发展。多西他赛(Dox)药物用于治疗PC,但在高浓度下会产生毒性或对患者的癌细胞产生耐药性。 PC的可能治疗方法建议使用载药纳米颗粒作为治疗剂。在这项研究中,纳米金刚石(ND's)被用作将Dox递送至PC细胞的载体。使用EDC / NHS化学方法将ND与Dox和Dox以及RGD肽偶联。使用ND荧光素跟踪PC3细胞中的ND,这表明ND孵育24小时后位于细胞核中。药物释放试验显示24小时内从NDs释放出92.3%的药物。微培养四氮唑测定(MTT)分析显示,孵育48小时后,ND在50μg/ mL时PC3细胞的活力为75%,而药物偶联的NDs为50%,表明它能有效地导致癌细胞死亡。孵育24小时后,对具有ND和缀合ND的PC3细胞进行基因表达分析。 NDR在PC细胞的许多基因中均表达上调。研究表明,NDs可用于PC3细胞的高效药物递送。

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