Enhanced Antitumor Efficacy by a Cascade of Reactive Oxygen Species Generation and Drug Release

2019 ◽  
Vol 131 (41) ◽  
pp. 14900-14905 ◽  
Author(s):  
Sheng Wang ◽  
Guocan Yu ◽  
Zhantong Wang ◽  
Orit Jacobson ◽  
Li‐Sen Lin ◽  
...  
2019 ◽  
Vol 58 (41) ◽  
pp. 14758-14763 ◽  
Author(s):  
Sheng Wang ◽  
Guocan Yu ◽  
Zhantong Wang ◽  
Orit Jacobson ◽  
Li‐Sen Lin ◽  
...  

2021 ◽  
Author(s):  
Ning Wang ◽  
Chenyu Liu ◽  
Weihe Yao ◽  
Hengjun Zhou ◽  
Simiao Yu ◽  
...  

Reactive oxygen species (ROS) are not only used as a therapeutic reagent in chemodynamic therapy (CDT), to stimulate the release of drugs, they can also be used to achieve a combined effect of CDT and chemotherapy to enhance anticancer effects.


2019 ◽  
Vol 6 (5) ◽  
pp. 1801986 ◽  
Author(s):  
Sheng Wang ◽  
Zhantong Wang ◽  
Guocan Yu ◽  
Zijian Zhou ◽  
Orit Jacobson ◽  
...  

The eff ect of the non-opiate analog of leu-enkephalin (peptide NALE: Phe – D – Ala – Gly – Phe – Leu – Arg) on the reactive oxygen species generation in the heart of albino rats in the early postnatal period was studied. Peptide NALE was administered intraperitoneally in the dose of 100 μ/kg daily from 2 to 6 days of life. Reactive oxygen species generation was assessed by chemiluminescence in the heart homogenates of 7-day-old animals. Decreasing of reactive oxygen species generation nearly by 30 % and an increasing in antioxidant system activity by the 20-27 %, compared with the control parameters, were found. The antioxidant eff ect of peptide NALE is associated with the presence of the amino acid Arg in the structure of the peptide. An analogue of NALE peptide, devoid of Arg (peptide Phe – D – Ala – Gly – Phe – Leu – Gly), had a signifi cant lower antioxidant eff ect. The NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the dose 50 mg/kg, administered with NALE peptide, reduced the severity of the NALE antioxidant eff ect. The results of the study suggest that the pronounced antioxidant eff ect of NALE peptide in the heart of albino rats, at least in part, is due to the interaction with the nitric oxide system.


2020 ◽  
Vol 22 (1) ◽  
pp. 154
Author(s):  
Fasih Bintang Ilhami ◽  
Kai-Chen Peng ◽  
Yi-Shiuan Chang ◽  
Yihalem Abebe Alemayehu ◽  
Hsieh-Chih Tsai ◽  
...  

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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