1. Nitric oxide-releasing nanoparticles improve doxorubicin anticancer activity
- Author
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Alimoradi H, Greish K, Barzegar-Fallah A, Alshaibani L, and Pittalà V
- Subjects
Biological barriers ,nanoparticles ,nitric oxide ,doxorubicin ,synergistic cytotoxicity ,SMA-tDodSNO ,Medicine (General) ,R5-920 - Abstract
Houman Alimoradi,1,* Khaled Greish,2,3,* Anita Barzegar-Fallah,1 Lama Alshaibani,2 Valeria Pittalà4 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2College of Medicine and Medical Sciences, Department of Molecular Medicine, and Nanomedicine Unit, Princess Al-Jawhara Centre for Molecular Medicine and Inherited Disorders, Arabian Gulf University, Manama, Kingdom of Bahrain; 3Department of Oncology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 4Department of Drug Science, University of Catania, Catania, Italy *These authors contributed equally to this work Purpose: Anticancer drug delivery systems are often limited by hurdles, such as off-target distribution, slow cellular internalization, limited lysosomal escape, and drug resistance. To overcome these limitations, we have developed a stable nitric oxide (NO)-releasing nanoparticle (polystyrene-maleic acid [SMA]-tert-dodecane S-nitrosothiol [tDodSNO]) with the aim of enhancing the anticancer properties of doxorubicin (Dox) and a Dox-loaded nanoparticle (SMA-Dox) carrier. Materials and methods: Effects of SMA-tDodSNO and/or in combination with Dox or SMA-Dox on cell viability, apoptosis, mitochondrial membrane potential, lysosomal membrane permeability, tumor tissue, and tumor growth were studied using in vitro and in vivo model of triple-negative breast cancer (TNBC). In addition, the concentrations of SMA-Dox and Dox in combination with SMA-tDodSNO were measured in cells and tumor tissues. Results: Combination of SMA-tDodSNO and Dox synergistically decreased cell viability and induced apoptosis in 4T1 (TNBC cells). Incubation of 4T1 cells with SMA-tDodSNO (40 µM) significantly enhanced the cellular uptake of SMA-Dox and increased Dox concentration in the cells resulting in a twofold increase (P
- Published
- 2018