Theranostic Prodrug Vesicles for Reactive Oxygen Species-Triggered Ultrafast Drug Release and Local-Regional Therapy of Metastatic Triple-Negative Breast Cancer

2017 ◽  
Vol 27 (46) ◽  
pp. 1703674 ◽  
Author(s):  
Fangyuan Zhou ◽  
Bing Feng ◽  
Tingting Wang ◽  
Dangge Wang ◽  
Zhirui Cui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Drug Release ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Regional Therapy

scholarly journals Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer

2021 ◽  
Vol 22 (14) ◽  
pp. 7439
Author(s):  
Kevin J Lee ◽  
Griffin Wright ◽  
Hannah Bryant ◽  
Leigh Ann Wiggins ◽  
Valeria L. Dal Zotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Vitamin D ◽  
Triple Negative Breast Cancer ◽  
Vitamin D3 ◽  
Cardiac Tissue ◽  
Triple Negative ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Quinone Oxidoreductase

Background: Doxorubicin (Dox) is a first-line treatment for triple negative breast cancer (TNBC), but its use may be limited by its cardiotoxicity mediated by the production of reactive oxygen species. We evaluated whether vitamin D may prevent Dox-induced cardiotoxicity in a mouse TNBC model. Methods: Female Balb/c mice received rodent chow with vitamin D3 (1500 IU/kg; vehicle) or chow supplemented with additional vitamin D3 (total, 11,500 IU/kg). the mice were inoculated with TNBC tumors and treated with intraperitoneal Dox (6 or 10 mg/kg). Cardiac function was evaluated with transthoracic echocardiography. The cardiac tissue was evaluated with immunohistochemistry and immunoblot for levels of 4-hydroxynonenal, NAD(P)H quinone oxidoreductase (NQO1), C-MYC, and dynamin-related protein 1 (DRP1) phosphorylation. Results: At 15 to 18 days, the mean ejection fraction, stroke volume, and fractional shortening were similar between the mice treated with vitamin D + Dox (10 mg/kg) vs. vehicle but significantly greater in mice treated with vitamin D + Dox (10 mg/kg) vs. Dox (10 mg/kg). Dox (10 mg/kg) increased the cardiac tissue levels of 4-hydroxynonenal, NQO1, C-MYC, and DRP1 phosphorylation at serine 616, but these increases were not observed with vitamin D + Dox (10 mg/kg). A decreased tumor volume was observed with Dox (10 mg/kg) and vitamin D + Dox (10 mg/kg). Conclusions: Vitamin D supplementation decreased Dox-induced cardiotoxicity by decreasing the reactive oxygen species and mitochondrial damage, and did not decrease the anticancer efficacy of Dox against TNBC.

scholarly journals Pentagamaboronon-0-Sorbitol Induces Apoptosis through Elevation of Reactive Oxygen Species in Triple Negative Breast Cancer Cells

2021 ◽  
Vol 12 (1) ◽  
pp. 46
Author(s):  
Ratna Dwi Ramadani ◽  
Rohmad Yudi Utomo ◽  
Adam Hermawan ◽  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Oxygen Species ◽  
Apoptosis Induction ◽  
Curcumin Analogue

Breast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords: Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation.

Fenton-reaction-stimulative nanoparticles decorated with a reactive-oxygen-species (ROS)-responsive molecular switch for ROS amplification and triple negative breast cancer therapy

2019 ◽  
Vol 7 (45) ◽  
pp. 7141-7151
Author(s):  
Jun Zhang ◽  
Tiantian Zuo ◽  
Xiao Liang ◽  
Yingxin Xu ◽  
Yifan Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Fenton Reaction ◽  
Triple Negative ◽  
Molecular Switch ◽  
Oxygen Species ◽  
Breast Cancer Therapy

P@P/H NPs were rapidly disintegrated in response to ROS, and this further enhanced ROS level in tumor cells via the Fenton reaction.

scholarly journals Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

2020 ◽  
Vol 22 (1) ◽  
pp. 154
Author(s):  
Fasih Bintang Ilhami ◽  
Kai-Chen Peng ◽  
Yi-Shiuan Chang ◽  
Yihalem Abebe Alemayehu ◽  
Hsieh-Chih Tsai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Drug Release ◽  
Visible Light ◽  
Cancer Cells ◽  
Laser Irradiation ◽  
Reactive Oxygen ◽  
Controlled Drug Release ◽  
Grand Challenge ◽  
Supramolecular System ◽  
Oxygen Species

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

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