Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme
| العنوان: | Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme |
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| المؤلفون: | Gabriele De Sena, Manlio Barbarisi, Salvatore Tafuto, Vincenzo Quagliariello, Rosario Vincenzo Iaffaioli, Luigi Schiavo, Emilia Armenia, Alfonso Barbarisi |
| المساهمون: | Barbarisi, M, Iaffaioli, R. V, Armenia, E, Schiavo, L, De Sena, G, Tafuto, S, Barbarisi, A, Quagliariello, V. |
| المصدر: | Journal of Cellular Physiology. 233:6550-6564 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, 0301 basic medicine, Polymers, Physiology, medicine.medical_treatment, Clinical Biochemistry, Brain tumor, Pharmacology, Hydrogel, Polyethylene Glycol Dimethacrylate, Targeted therapy, glioblastoma multiforme, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Temozolomide, medicine, Humans, Molecular Targeted Therapy, CD44, Hyaluronic Acid, Cytotoxicity, Cell Proliferation, Drug Carriers, Tumor microenvironment, biology, Interleukin-6, business.industry, Interleukin-8, Cell Biology, medicine.disease, nanohydrogel, Gene Expression Regulation, Neoplastic, Hyaluronan Receptors, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer cell, biology.protein, Nanoparticles, Quercetin, Nanocarriers, Glioblastoma, business, medicine.drug |
| الوصف: | Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment. Glioblastoma multiforme is the most common and aggressive primary brain cancer with only approximate to 3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment. |
| تدمد: | 1097-4652 0021-9541 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21238c351c6109abaac90e4c4fd506efTest https://doi.org/10.1002/jcp.26238Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....21238c351c6109abaac90e4c4fd506ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974652 00219541 |
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