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Tytuł pozycji:

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells.

Tytuł :
Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells.
Autorzy :
Wu PH; Department of Radiation Medicine.
Onodera Y; Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Hokkaido.
Ichikawa Y; Innovation Center, Aisin Seiki Co., Ltd., Aichi, Japan.; IMRA America, Inc., Ann Arbor, MI.
Rankin EB; Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University Medical Center, Stanford, CA, USA.
Giaccia AJ; Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University Medical Center, Stanford, CA, USA.
Watanabe Y; Innovation Center, Aisin Seiki Co., Ltd., Aichi, Japan.
Qian W; IMRA America, Inc., Ann Arbor, MI.
Hashimoto T; Department of Radiation Medicine.
Shirato H; Department of Radiation Medicine.; Research Center for Cooperative Projects, Graduate School of Medicine.; Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan.
Nam JM; Department of Radiation Medicine.; Research Center for Cooperative Projects, Graduate School of Medicine.; Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan.
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Źródło :
International journal of nanomedicine [Int J Nanomedicine] 2017 Jul 14; Vol. 12, pp. 5069-5085. Date of Electronic Publication: 2017 Jul 14 (Print Publication: 2017).
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: Auckland : DOVE Medical Press,
MeSH Terms :
Breast Neoplasms/*drug therapy
Breast Neoplasms/*radiotherapy
Integrins/*metabolism
Nanoparticles/*administration & dosage
Oligopeptides/*chemistry
Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/radiation effects ; Endosomes/drug effects ; Endosomes/metabolism ; Female ; Fibronectins/genetics ; Gold/chemistry ; Humans ; Nanoparticles/chemistry ; Oligopeptides/metabolism ; Polyethylene Glycols/chemistry ; Radiation-Sensitizing Agents/chemistry ; Radiation-Sensitizing Agents/pharmacology
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Contributed Indexing :
Keywords: breast cancer; fibronectin; gold nanoparticles; integrin; invasion; radiotherapy
Substance Nomenclature :
0 (Fibronectins)
0 (Integrins)
0 (Oligopeptides)
0 (Radiation-Sensitizing Agents)
3WJQ0SDW1A (Polyethylene Glycols)
7440-57-5 (Gold)
78VO7F77PN (arginyl-glycyl-aspartic acid)
Entry Date(s) :
Date Created: 20170902 Date Completed: 20171218 Latest Revision: 20181202
Update Code :
20210301
PubMed Central ID :
PMC5560413
DOI :
10.2147/IJN.S137833
PMID :
28860745
Czasopismo naukowe
Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg-Gly-Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5- and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy.

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