PMID- 33671292
OWN - NLM
STAT- MEDLINE
DCOM- 20210413
LR  - 20210413
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 17
TI  - PrP(C) Aptamer Conjugated-Gold Nanoparticles for Targeted Delivery of Doxorubicin 
      to Colorectal Cancer Cells.
LID - 10.3390/ijms22041976 [doi]
LID - 1976
AB  - 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.
FAU - Go, Gyeongyun
AU  - Go G
AD  - Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 
      31151, Korea.
AD  - Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang 
      University, Cheonan 31151, Korea.
FAU - Lee, Chang-Seuk
AU  - Lee CS
AUID- ORCID: 0000-0002-5905-800X
AD  - Department of ICT Environmental Health System, Graduate School, Soonchunhyang 
      University, Asan 31538, Korea.
FAU - Yoon, Yeo Min
AU  - Yoon YM
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul 04401, Korea.
FAU - Lim, Ji Ho
AU  - Lim JH
AD  - Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang 
      University, Cheonan 31151, Korea.
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul 04401, Korea.
FAU - Kim, Tae Hyun
AU  - Kim TH
AUID- ORCID: 0000-0002-0154-518X
AD  - Department of ICT Environmental Health System, Graduate School, Soonchunhyang 
      University, Asan 31538, Korea.
AD  - Department of Chemistry, Soonchunhyang University, Asan 31538, Korea.
FAU - Lee, Sang Hun
AU  - Lee SH
AUID- ORCID: 0000-0002-6713-8229
AD  - Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 
      31151, Korea.
AD  - Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang 
      University, Cheonan 31151, Korea.
AD  - Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 
      Seoul 04401, Korea.
LA  - eng
GR  - 2019M3A9H1103495/Bio & Medical Technology Development Program of the National 
      Research Foundation (NRF) funded by the Korean government (MSIT)/
PT  - Journal Article
DEP - 20210217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (PPARGC1A protein, human)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Prion Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 7440-57-5 (Gold)
RN  - 80168379AG (Doxorubicin)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Aptamers, Nucleotide/*chemistry
MH  - Catalase/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/*drug therapy
MH  - Doxorubicin/*administration & dosage/pharmacology/*therapeutic use
MH  - *Drug Delivery Systems
MH  - Gold/*chemistry
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Metal Nanoparticles/*chemistry
MH  - Mitochondria/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Prion Proteins/*chemistry
MH  - Reactive Oxygen Species/metabolism
MH  - Spheroids, Cellular/drug effects/metabolism
MH  - Superoxide Dismutase/metabolism
PMC - PMC7922473
OTO - NOTNLM
OT  - PrPC
OT  - PrPC aptamer
OT  - colorectal cancer
OT  - doxorubicin
OT  - drug delivery
OT  - gold nanoparticle
COIS- The authors declare no conflict of interest. The funders had no role in the study 
      design, collection and analysis of data, decision to publish, or preparation of 
      the manuscript.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/14 06:00
PMCR- 2021/02/17
CRDT- 2021/03/06 01:10
PHST- 2021/01/02 00:00 [received]
PHST- 2021/02/11 00:00 [revised]
PHST- 2021/02/13 00:00 [accepted]
PHST- 2021/03/06 01:10 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/14 06:00 [medline]
PHST- 2021/02/17 00:00 [pmc-release]
AID - ijms22041976 [pii]
AID - ijms-22-01976 [pii]
AID - 10.3390/ijms22041976 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 17;22(4):1976. doi: 10.3390/ijms22041976.