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Tytuł pozycji:

The Use of TAT Peptide-Functionalized Graphene as a Highly Nuclear-Targeting Carrier System for Suppression of Choroidal Melanoma.

Tytuł:
The Use of TAT Peptide-Functionalized Graphene as a Highly Nuclear-Targeting Carrier System for Suppression of Choroidal Melanoma.
Autorzy:
Shan S; Laboratory of Nanoscale Biosensing and Bioimaging, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, 270 Xueyuanxi Road, Wenzhou 325027, China. shan_.
Jia S; Laboratory of Nanoscale Biosensing and Bioimaging, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, 270 Xueyuanxi Road, Wenzhou 325027, China. .
Lawson T; ARC Center of Excellence for Nanoscale Bio Photonics, Macquarie University, Sydney, NSW 2109, Australia. .
Yan L; Laboratory of Nanoscale Biosensing and Bioimaging, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, 270 Xueyuanxi Road, Wenzhou 325027, China. .
Lin M; Laboratory of Nanoscale Biosensing and Bioimaging, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, 270 Xueyuanxi Road, Wenzhou 325027, China. .
Liu Y; Laboratory of Nanoscale Biosensing and Bioimaging, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, 270 Xueyuanxi Road, Wenzhou 325027, China. .
Źródło:
International journal of molecular sciences [Int J Mol Sci] 2019 Sep 10; Vol. 20 (18). Date of Electronic Publication: 2019 Sep 10.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
Choroid Neoplasms/*drug therapy
Drug Delivery Systems/*methods
Graphite/*chemistry
Melanoma/*drug therapy
Mitomycin/*administration & dosage
Peptides/*chemistry
Antibiotics, Antineoplastic/administration & dosage ; Antibiotics, Antineoplastic/chemistry ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Cell Nucleus/ultrastructure ; Choroid Neoplasms/metabolism ; Choroid Neoplasms/pathology ; Drug Carriers/chemistry ; Humans ; Melanoma/metabolism ; Melanoma/pathology ; Microscopy, Electron, Transmission ; Mitomycin/chemistry ; Nanostructures/administration & dosage ; Nanostructures/chemistry ; Nanostructures/ultrastructure ; tat Gene Products, Human Immunodeficiency Virus/chemistry
References:
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Grant Information:
LR17H180001, LY19H180002 Natural Science Foundation of Zhejiang Province; 51433005 National Natural Science Foundation of China
Contributed Indexing:
Keywords: choroidal melanoma; graphene; mitomycin C (MMC); nuclear targeting drug delivery; trans-activating transcriptional activator (TAT) peptide
Substance Nomenclature:
0 (Antibiotics, Antineoplastic)
0 (Drug Carriers)
0 (Peptides)
0 (tat Gene Products, Human Immunodeficiency Virus)
50SG953SK6 (Mitomycin)
7782-42-5 (Graphite)
Entry Date(s):
Date Created: 20190913 Date Completed: 20200210 Latest Revision: 20231014
Update Code:
20240105
PubMed Central ID:
PMC6769650
DOI:
10.3390/ijms20184454
PMID:
31509978
Czasopismo naukowe
Tumorous metastasis is a difficult challenge to resolve for researchers and for clinicians. Targeted delivery of antitumor drugs towards tumor cells' nuclei can be a practical approach to resolving this issue. This work describes an efficient nuclear-targeting delivery system prepared from trans-activating transcriptional activator (TAT) peptide-functionalized graphene nanocarriers. The TAT peptide, originally observed in a human immunodeficiency virus 1 (HIV-1), was incorporated with graphene via an edge-functionalized ball-milling method developed by the author's research group. High tumor-targeting capability of the resulting nanocarrier was realized by the strong affinity between TAT and the nuclei of cancer cells, along with the enhanced permeability and retention (EPR) effect of two-dimensional graphene nanosheets. Subsequently, a common antitumor drug, mitomycin C (MMC), was covalently linked to the TAT-functionalized graphene (TG) to form a nuclear-targeted nanodrug MMC-TG. The presence of nanomaterials inside the nuclei of ocular choroidal melanoma (OCM-1) cells was shown using transmission electron microscopy (TEM) and confocal laser scanning microscopy. In vitro results from a Transwell co-culture system showed that most of the MMC-TG nanodrugs were delivered in a targeted manner to the tumorous OCM-1 cells, while a very small amount of MMC-TG was delivered in a non-targeted manner to normal human retinal pigment epithelial (ARPE-19) cells. TEM results further confirmed that apoptosis of OCM-1 cells was started from the lysis of nuclear substances, followed by the disappearance of nuclear membrane and cytoplasm. This suggests that the as-synthesized MMC-TG is a promising nuclear-target nanodrugfor resolution of tumorous metastasis issues at the headstream.
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