Rezvan Yazdian-Robati1, Mohammad Ramezani2, Seyed Hamid Jalalian2,3, Khalil Abnous4, Seyed Mohammad Taghdisi5. 1. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Academic Center for Education, Culture and Research (ACECR)-Mashhad Branch, Mashhad, Iran. 4. Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. abnouskh@mums.ac.ir. 5. Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. taghdisihm@mums.ac.ir.
Abstract
PURPOSE: The clinical use of Epirubicin (Epi), as an anthracycline drug, is limited because of its cardiotoxicity. Here, an Epirubicin (Epi)-modified polyvalent aptamer system (MPAS) conjugate was developed for the treatment of both murine colon carcinoma cells (C26) and breast cancer cells (MCF-7). METHODS: Epi-MPAS conjugate formation was evaluated by fluorometric analysis. Release profiles of Epi from the developed conjugate were analyzed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) C26 and MCF-7 (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, MPAS and Epi-MPAS conjugate. Internalization was assessed by fluorescence imaging and flow cytometry analysis. The designed conjugate was used for prohibition of tumor growth in vivo. RESULTS: Release of Epi from the Epi-MPAS conjugated was pH-dependent (more release at pH 5.5). Flow cytometry analysis and MTT assay showed that Epi-MPAS conjugate could significantly enhance the cellular uptake of Epi and increase its cytotoxicity in target cells as compared with non-targeted cell (CHO). Additionally, this complex could efficiently prohibit the tumor growth in vivo. CONCLUSION: In conclusion, the developed drug delivery system had the characteristics of efficient Epi loading, pH-dependent drug release and tumor targeting in vitro and in vivo.
PURPOSE: The clinical use of Epirubicin (Epi), as an anthracycline drug, is limited because of its cardiotoxicity. Here, an Epirubicin (Epi)-modified polyvalent aptamer system (MPAS) conjugate was developed for the treatment of both murinecolon carcinoma cells (C26) and breast cancer cells (MCF-7). METHODS: Epi-MPAS conjugate formation was evaluated by fluorometric analysis. Release profiles of Epi from the developed conjugate were analyzed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) C26 and MCF-7 (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, MPAS and Epi-MPAS conjugate. Internalization was assessed by fluorescence imaging and flow cytometry analysis. The designed conjugate was used for prohibition of tumor growth in vivo. RESULTS: Release of Epi from the Epi-MPAS conjugated was pH-dependent (more release at pH 5.5). Flow cytometry analysis and MTT assay showed that Epi-MPAS conjugate could significantly enhance the cellular uptake of Epi and increase its cytotoxicity in target cells as compared with non-targeted cell (CHO). Additionally, this complex could efficiently prohibit the tumor growth in vivo. CONCLUSION: In conclusion, the developed drug delivery system had the characteristics of efficient Epi loading, pH-dependent drug release and tumor targeting in vitro and in vivo.
Entities:
Keywords:
aptamer; drug delivery; epirubicin; polyvalent
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