期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms22041976
关键词
PrP(C); PrP(C) aptamer; colorectal cancer; gold nanoparticle; doxorubicin; drug delivery
资金
- National Research Foundation of Korea (NRF) - Korea Government (MSIT) [2016R1D1A3B01007727, NRF2020R1A2C1014918]
This study developed PrP(C)-Apt-functionalized doxorubicin-oligomer-AuNPs for targeted drug delivery to colorectal cancer cells. Treatment with these nanoparticles induced reactive oxygen species generation and inhibited mitochondrial functions in CRC cells, leading to decreased proliferation and increased apoptosis compared to free Dox. These findings suggest that PrP(C)-Apt DOA may be a more effective treatment for CRC than traditional anticancer drugs.
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 PrP(C), which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrP(C)-targeting DDSs for targeted drug delivery to CRC. In this study, PrP(C) aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrP(C)-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrP(C)-Apt-functionalized doxorubicin-oligomer-AuNPs (PrP(C)-Apt DOA). The PrP(C)-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrP(C)-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrP(C)-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, PrP(C)-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrP(C)-Apt DOA targeting could effectively deliver Dox to CRC cells. PrP(C)-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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