PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells |
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Authors: | Gyeongyun Go Chang-Seuk Lee Yeo Min Yoon Ji Ho Lim Tae Hyun Kim Sang Hun Lee |
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Affiliation: | 1.Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea;2.Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea;3.Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan 31538, Korea;4.Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea;5.Department of Chemistry, Soonchunhyang University, Asan 31538, Korea |
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Abstract: | Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC); however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrPC, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrPC-targeting DDSs for targeted drug delivery to CRC. In this study, PrPC aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrPC-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrPC-Apt-functionalized doxorubicin-oligomer-AuNPs (PrPC-Apt DOA). The PrPC-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrPC-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrPC-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrPC-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrPC-Apt DOA targeting could effectively deliver Dox to CRC cells. PrPC-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox. |
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Keywords: | PrPC PrPC aptamer colorectal cancer gold nanoparticle doxorubicin drug delivery |
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