Double-receptor-targeting multifunctional iron oxide nanoparticles drug delivery system for the treatment and imaging of prostate cancer

被引:48
作者
Ahmed, Md Shakir Uddin [1 ]
Bin Salam, Ahmad [1 ]
Yates, Clayton [1 ]
Willian, Kyle [2 ]
Jaynes, Jesse [3 ]
Turner, Timothy [4 ]
Abdalla, Mohamed O. [5 ]
机构
[1] Tuskegee Univ, Dept Biol, Tuskegee, AL 36088 USA
[2] Auburn Univ, Dept Chem & Biochem, Auburn, AL 36849 USA
[3] Tuskegee Univ, Dept Environm Sci, Tuskegee, AL 36088 USA
[4] Jackson State Univ, Dept Biol, Jackson, MS USA
[5] Tuskegee Univ, Dept Chem, 102 Armstrong Hall, Tuskegee, AL 36088 USA
关键词
LHRH-R; uPAR; prostate cancer; iron oxide nanoparticles; targeted drug delivery; HORMONE-RELEASING HORMONE; CELL-LINE LNCAP; MAGNETIC NANOPARTICLES; PLASMINOGEN-ACTIVATOR; THERAPY; EXPRESSION; HETEROGENEITY; PEPTIDES; AGONISTS; LHRH;
D O I
10.2147/IJN.S139011
中图分类号
TB3 [工程材料学];
学科分类号
082905 [生物质能源与材料];
摘要
As an alternative therapeutic treatment to reduce or eliminate the current side effects associated with advanced prostate cancer (PCa) chemotherapy, a multifunctional double-receptor-targeting iron oxide nanoparticles (IONPs) (luteinizing hormone-releasing hormone receptor [LHRH-R] peptide-and urokinase-type plasminogen activator receptor [uPAR] peptide-targeted iron oxide nanoparticles, LHRH-AE105-IONPs) drug delivery system was developed. Two tumor-targeting peptides guided this double-receptor-targeting nanoscale drug delivery system. These peptides targeted the LHRH-R and the uPAR on PCa cells. Dynamic light scattering showed an increase in the hydrodynamic size of the LHRH-AE105-IONPs in comparison to the non-targeted iron oxide nanoparticles (NT-IONPs). Surface analysis showed that there was a decrease in the zeta potential values for drug-loaded LHRH-AE105-IONPs compared to the NT-IONPs. Prussian blue staining demonstrated that the LHRH-AE105-IONPs were internalized efficiently by the human PCa cell line, PC-3. In vitro, magnetic resonance imaging (MRI) results confirmed the preferential binding and accumulation of LHRH-AE105-IONPs in PC-3 cells compared to normal prostate epithelial cells (RC77N/E). The results also showed that LHRH-AE105-IONPs significantly maintained T-2 MRI contrast effects and reduced T-2 values upon internalization by PC-3 cells. These paclitaxel-loaded double-receptor-targeting IONPs also showed an approximately twofold reduction in PC-3 cell viability compared to NT-IONPs.
引用
收藏
页码:6973 / 6984
页数:12
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