Metformin- mesoporous silica nanoparticles loaded electrospun thermo-responsive copolymer for targeted ovarian cancer therapy

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 309

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شناسه ملی سند علمی:

ICIBS01_251

تاریخ نمایه سازی: 2 آذر 1399

چکیده مقاله:

Background: Breast cancer is one of the most common malignancies in women, and its incidence has increased in recent year. Although Metformin (Met) has good biocompatibility, its clinical applicability is limited by poor solubility in water, low stability, and a short half-life in the circulation. Nanocarriers have attracted broad attention in cancer therapy because of their ability to carry drugs preferentially into cancer tissue, but their application is still limited due to the systemic toxicity and low delivery efficacy of intravenously delivered chemotherapeutics. In this study, we develop a localized drug delivery device with combination of a mesoporous silica nanoparticles and implantable polymeric nanofibers.Methods: The fibers are produced by electrospinning copolymers of N-isopropylacrylamide (NIPAAm) and N-hydroxymethylacrylamide (HMAAm). The OH groups of HMAAm are subsequently crosslinked by thermal curing. The copolymers were successfully fabricated into a well-defined nanofibrous structure. Moreover, the ‘on–off’ switchable release of MET from the crosslinked NFs was observed. Cytotoxic assays were evaluated in SKOV3 cells treated with the MTT assay. Also, real-time polymerase chain reaction (Real-Time PCR) was used to determine the gene expression levels of hTERT. Results: In vitro cytotoxicity assay using MTT revealed that the MET and MET/MSN@P(NIPAM-co-MAA) nanofibers exhibited a dose- and time- dependent cytotoxic effect against Skov3 cells. qPCR findings showed that the MET/MSN@P(NIPAM-co-MAA) nanofibers also down-regulated the expression levels of hTERT at all used concentrations compared with the drugs used alone after 28 h treatment.Conclusion: Our results reveled that incorporation of smart properties into NFs takes advantage of their extremely large surface area and porosity and is expected to provide a simple platform for on–off drug delivery. Also, these results indicate that MET/MSN@P(NIPAM-co-MAA) nanofibers are biocompatible and effectively deliver drugs to the tumors and suppress tumor growth.

نویسندگان

Shadi Samadzadeh

Department of Chemistry, Faculty of Science, Tabriz Branch- Islamic Azad University, Tabriz, Iran

Mehdi Dadashpour

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Yones Pilehvar-Soltanhadi

Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

Hanieh Mousazadeh

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran