The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment
Joint Authors
Zhu, Yi-Zhi
Xu, Di
Liu, Zhen
Tian, Tian
Deng, Fei
Tang, Wen-Juan
Wu, Yang
Zhang, Wei
Tang, Jin-Hai
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-05-26
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Triple-negative breast cancer (TNBC) is a highly malignant tumor.
At present, there are still no targeted drugs for TNBC.
Clinical chemotherapeutic drugs, such as doxorubicin (DOX), have the characteristic of nontargeted distribution in treatment of TNBC, causing severe side effects.
Therefore, new target treatment strategies for TNBC are of urgent need.
It was speculated that glutamine could be a potential target because it is in high demand by TNBC.
In this study, we found that the transporter for glutamine, ASCT2 (solute carrier family 1 member 5 (SLC1A5)), is highly expressed in TNBC by analysis of data from The Cancer Genome Atlas (TCGA) and experiments in vitro.
Based on this, glutamine was grafted onto a polymeric drug carrier in order to develop a tumor-targeting drug delivery system for treatment of TNBC.
Firstly, pH-responsive glutamine-PEG5000-b-PAE10000 (Gln-PEG-b-PAE) copolymers were synthesized using Fmoc-PEG5000-b-PAE10000 (Fmoc-PEG-b-PAE) copolymers.
Then, Gln-PEG-b-PAE@DOX micelles were prepared by loading DOX to Gln-PEG-b-PAE copolymer using a solvent casting technology.
In vitro, Gln-PEG-b-PAE@DOX micelles exhibited pH-dependent micellization-decellularization behavior; namely, they can rapidly release DOX in acidic environment of pH 6.0 but release very slowly in physiological condition.
Moreover, glutamine competition experiment showed that Gln-PEG-b-PAE@DOX micelles had the ability to target MDA-MB-231 cells.
Compared to free DOX, Gln-PEG-b-PAE@DOX micelles had significantly greater cytotoxic effect and antiproliferative activity against MDA-MB-231 cells.
In vivo, compared to free DOX and mPEG-b-PAE@DOX micelles, Gln-PEG-b-PAE@DOX micelles significantly inhibited tumor growth in tumor-bearing mice.
Therefore, Gln-PEG-b-PAE@DOX micelles, as a tumor-targeting drug delivery system, may provide a new method for the treatment of TNBC.
American Psychological Association (APA)
Zhu, Yi-Zhi& Xu, Di& Liu, Zhen& Tian, Tian& Deng, Fei& Tang, Wen-Juan…[et al.]. 2020. The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment. Journal of Nanomaterials،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1188451
Modern Language Association (MLA)
Zhu, Yi-Zhi…[et al.]. The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment. Journal of Nanomaterials No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1188451
American Medical Association (AMA)
Zhu, Yi-Zhi& Xu, Di& Liu, Zhen& Tian, Tian& Deng, Fei& Tang, Wen-Juan…[et al.]. The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment. Journal of Nanomaterials. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1188451
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1188451