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Abstract Title:

Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer.

Abstract Source:

Drug Dev Ind Pharm. 2018 Jun ;44(6):982-987. Epub 2018 Jan 25. PMID: 29325460

Abstract Author(s):

Seyed Hossein Rajabnejad, Ahad Mokhtarzadeh, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Bibi Marjan Razavi

Article Affiliation:

Seyed Hossein Rajabnejad

Abstract:

Melittin, a small water-soluble cationic amphipathicα-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer-melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (nucleolin positive) and L929 (nucleolin negative) was studied using MTT and Annexin V flow cytometry methods. Aptamer-melittin conjugate formation was confirmed by gel electrophoresis. Hemolytic effect of aptamer-melittin conjugate was compared to melittin alone. The aptamer-melittin conjugate showed efficient cell uptake and was more cytotoxic in A549 cells than melittin (p < .001). This complex was less toxic in control cells. Competitive inhibition assay confirmed that aptamer-melittin complex delivery occurred through receptor-ligand interaction on the cell surface. Moreover, aptamer-melittin showed a significantly less hemolytic activity as compared with free melittin. This study showed that melittin could be specifically delivered to A549 cells when it was covalently conjugated to antinucleolin aptamer (AS1411) in vitro. This system can reduce the cytotoxic effects of melittin on cells with no nucleolin receptor overexpression which comprise most of normalcells such as L929 cells.

Study Type : In Vitro Study

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