مرکز تحقیقات بيولوژي سلولي و ملكولي
۱۳۹۸ دوشنبه ۲ ارديبهشت
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تاریخ: 1397/12/08 تعداد بازدید: 193
چاپ مقاله جديد توسط خانم دكتر رضوان يزديان رباطي عضو هيئت علمي مركز در مجله Drug Dev Ind Pharm
Drug Dev Ind Pharm. 2019 Jan 11:1-8.
Drug Dev Ind Pharm. 2019 Jan 11:1-8. doi: 10.1080/03639045.2019.1569029. [Epub ahead of print]

Smart aptamer-modified calcium carbonate nanoparticles for controlled release and targeted delivery of epirubicin and melittin into cancer cells in vitro and in vivo.

Author information

1
a Molecular and Cell biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences , Sari , Iran.
2
b Department of Pharmaceutical Biotechnology , School of Pharmacy, Mashhad University of Medical Sciences , Mashhad , Iran.
3
c Pharmaceutical Research Center , Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad , Iran.
4
d Faculty of Medicine, Department of Immunology , Immunology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.
5
e Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Department of Pharmacognosy , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
6
f Targeted Drug Delivery Research Center , Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad , Iran.

Abstract

To explore the effect of combination therapy of epirubicin (Epi) and melittin (Mel) to cancer cells, calcium carbonate nanoparticles (CCN), as carriers, were developed which were modified with MUC1-Dimer aptamers as targeting agents. Both Epi and Mel were delivered at the same time to cancer cells overexpressing the target of MUC1 aptamer, mucin 1 glycoproteins (MCF7 and C26 cells). CCN were prepared with a water-in-oil emulsion method. Epi and Mel were separately encapsulated in CCN and the nanoparticles were modified with MUC1-Dimer aptamers. In vitro studies, including MTT assay, flow cytometry analysis and fluorescence imaging were applied to investigate the targeting and cell proliferation inhibition capabilities of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex in the target (MCF-7 and C26 cells) and nontarget (HepG2) cells. Also, the function of the developed complexes was analyzed using in vivo tumor growth inhibition. The release of Epi from MUC1-Dimer aptamer-CCN-Epi complex was pH-sensitive. Cellular uptake studies showed more internalization of the MUC1-Dimer aptamer-CCN-Epi complex into MCF-7 and C26 cells (target) compared to HepG2 cells (nontarget). Interestingly, the MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex indicated very low toxicity as compared to target cells. Moreover, co-delivery of Epi and Mel using the mixture of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex exhibited strong synergistic cytotoxicity in MCF-7 and C26 cells. Furthermore, the presented complexes had a better function to control tumor growth in vivo compared to free Epi.

 
 
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