scholarly journals A self-assembled RNA-triple helix hydrogel drug delivery system targeting 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.

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 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.


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 ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.


2014 ◽  
Vol 17 (3) ◽  
pp. 439 ◽  
Author(s):  
Wayne Goh ◽  
Inna Sleptsova-Freidrich ◽  
Nenad Petrovic

PURPOSE: Triple negative breast cancers (estrogen, progesterone and human epidermal growth factor 2 (HER2) receptor-negative) are among the most aggressive forms of cancers with limited treatment options. Doxorubicin is one of the agents found in many of the current cancer treatment protocols, although its use is limited by dose-dependent cardiotoxicity. This work investigates one of the ways to suppress cancer growth by inhibiting tumor cell ability to remove acid accumulated during its metabolism by proton pump inhibitor esomeprazole (a drug with extensive clinical use) which could serve as an addition to doxorubicin therapy. METHODS: In this work, we have investigated growth suppression of triple-negative breast cancer cells MDA-MB-468 by esomeprazole and doxorubicin by trypan blue exclusion assay. Measurement of acidification of treated cancer cells was performed using intracellular pH-sensitive probe, BCECF-AM. Finally, expression of gastric type proton pump (H+/K+ ATPase, a target for esomeprazole) on MDA-MB-468 cells was detected by immunofluorescence and Western blotting. RESULTS: We have found that esomeprazole suppresses growth of triple-negative breast cancer cell in vitro in a dose-dependent manner through increase in their intracellular acidification. In contrast, esomeprazole did not have significant effect on non-cancerous breast epithelial MCF-10A cells. Esomeprazole increases doxorubicin effects suggesting that dual treatments might be possible. In addition, response of MDA-MB-468 cells to esomeprazole could be mediated by gastric type proton pump (H+/K+ ATPase) in cancer cells contrary to previous beliefs that this proton pump expression is restricted to parietal cells of the stomach epithelia. CONCLUSION: This study provides first evidence that adjunct use of esomeprazole in breast cancer treatment might be a possible to combat adverse effects of doxorubicin and increase its effectiveness. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.


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