scholarly journals The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yi-Zhi Zhu ◽  
Di Xu ◽  
Zhen Liu ◽  
Tian Tian ◽  
Fei Deng ◽  
...  

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.

Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 981-1000
Author(s):  
C Ethan Byrne ◽  
Carlos E Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  

Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic- co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.


2019 ◽  
Vol 7 (23) ◽  
pp. 3724-3736 ◽  
Author(s):  
Changliang Liu ◽  
Houqian Gao ◽  
Zijian Zhao ◽  
Iman Rostami ◽  
Chen Wang ◽  
...  

A dual-functional drug delivery system based on the conjugation of PAMAM dendrimer with EBP-1 and TAT peptide was established for the therapy of triple-negative breast cancer.


2020 ◽  
Vol 8 (16) ◽  
pp. 3527-3533 ◽  
Author(s):  
Lairong Ding ◽  
Junwei Li ◽  
Changrong Wu ◽  
Feng Yan ◽  
Xuemei Li ◽  
...  

A novel RNA-triple-helix hydrogel for treatment of triple negative breast cancers (TNBCs) by incorporating RNA-triple-helix and siRNA duplexes of CXCR4 into the same RNA nanoparticles was developed, without the synthetic polycationic reagents.


2020 ◽  
Author(s):  
Sophia Antimisiaris ◽  
Helen Lamprou ◽  
Spyridon Mourtas ◽  
Maria Mantzari ◽  
Antonia Maraziotis ◽  
...  

2019 ◽  
Author(s):  
Ethan Byrne ◽  
Carlos E. Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  

2019 ◽  
Vol 53 ◽  
pp. 101144 ◽  
Author(s):  
Simona Giarra ◽  
Noemi Lupo ◽  
Virginia Campani ◽  
Alfonso Carotenuto ◽  
Laura Mayol ◽  
...  

2021 ◽  
Vol 133 ◽  
pp. 111053
Author(s):  
Dorota Bartusik-Aebisher ◽  
Grzegorz Chrzanowski ◽  
Zuzanna Bober ◽  
David Aebisher

2019 ◽  
Vol 33 (10) ◽  
pp. 1394-1406 ◽  
Author(s):  
Juan Cai ◽  
Keyang Qian ◽  
Xueliang Zuo ◽  
Wuheng Yue ◽  
Yinzhu Bian ◽  
...  

Docetaxel (TXT) is acknowledged as one of the most important chemotherapy agents for gastric cancer (GC). PI3K/AKT signaling is frequently activated in GC, and its inhibitor LY294002 exerts potent antitumor effects. However, the hydrophobicity of TXT and the poor solubility and low bioavailability of LY294002 limit their clinical application. To overcome these shortcomings, we developed poly(lactic acid/glycolic) (PLGA) nanoparticles loaded with TXT and LY294002. PLGA facilitated the accumulation of TXT and LY294002 at the tumor sites. The in vitro functional results showed that PLGA(TXT+LY294002) exhibited controlled-release and resulted in a markedly reduced proliferative capacity and an elevated apoptosis rate. An in vivo orthotopic GC mouse model and xenograft mouse model confirmed the anticancer superiority and tumor-targeting feature of PLGA(TXT+LY294002). Histological analysis indicated that PLGA(TXT+LY294002) was biocompatible and had no toxicity to major organs. Characterized by the combined slow release of TXT and LY294002, this novel PLGA-based TXT/LY294002 drug delivery system provides controlled release and tumor targeting and is safe, shedding light on the future of targeted therapy against GC.


2005 ◽  
Vol 288-289 ◽  
pp. 125-128 ◽  
Author(s):  
Shen Guo Wang ◽  
Qing Cai ◽  
Jian Zhong Bei ◽  
Wei Yun Shi ◽  
Li Xin Xie

In the article a kind biodegradable drug carrier (glycolide-co-lactide-co-caprolactone) tricomponent copolymer (PGLC) was synthesized by ring opening copolymerization of glycolide (GA), lactide (LA) and ε-caprolactone (CL), and was used to manufacture an implantable drug preparation---Cyclosporine-PGLC drug delivery system (Cs-PGLC DDS).The Cs could slowly release from the Cs-PGLC DDS near linearly and last for a long time in vitro. A clinically significant Cs concentration in the cornea and anterior chamber could be achieved by implanting the Cs-PGLC DDS in anterior chamber. It was demonstrated that the Cs-PGLC DDS is a long-effective intraocular immunosuppressive agent for remaining corneal allograft clear and significantly prolong its survival time.


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