APTAMER-BASED TARGETED DELIVERY OF MIRNA LET-7D TO GASTRIC CANCER CELLS AS A NOVEL ANTI-TUMOR THERAPEUTIC AGENT

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DAEI PUYAN; RAMEZANPOUR MAHSA; KHANAKI KOROSH; TABARZAD MARYAM; NIKOKAR IRAJ; HEDAYATI CH. MOJTABA; ELMI ALI

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Journal: Iranian Journal of Pharmaceutical Research Year:2018 | Volume:17 | Issue:4 Page(s): 1537-1549

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Title

APTAMER-BASED TARGETED DELIVERY OF MIRNA LET-7D TO GASTRIC CANCER CELLS AS A NOVEL ANTI-TUMOR THERAPEUTIC AGENT

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Keywords

NUCLEOLIN SPECIFIC APTAMER (APTNCL)

MIRNA LET-7D

GASTRIC CANCER

CONJUGATE

TARGETED DELIVERY

Abstract

miRNAs as one of the potential therapeutic agents have been recently considered for cancer treatment. AS1411 (aptNCL) is a DNA aptamer specifically binding to nucleolin protein on the cancer cell surface with antiproliferative effect. The aim of the study was to develop a CONJUGATE consisting of aptNCL (as TARGETED DELIVERY of therapeutic agent) and MIRNA LET-7D (as a tumor suppressor) using two different linking methods and also to evaluate the potential effect of the CONJUGATEs on the proliferation of GASTRIC CANCER (MKN-45) cell line compared to negative control cell line of human dermal fibroblast (HDF). Conjugation was performed covalently by SM (PEG)2 as a bifunctional crosslinker (conjugate-1) and noncovalently, using 19bp complementary sticky end sequences (conjugate-2). Nucleolin positive MKN-45 and nucleolin negative HDF cells were cultured and treated with the CONJUGATEs. Then, the changes in let-7d expression and cell proliferation were determined using Real-time PCR and MTT methods, respectively. In MKN-45 cells, the CONJUGATEs caused significant increase in let7-d uptake compared with HDF cells (P=0.0001). The CONJUGATE-1, likely due to its higher stability compared with the CONJUGATE-2, led to significantly more increase in intracellular let- 7d in MKN-45 cells (30 fold versus 15 fold, respectively, P=0.0001). The CONJUGATEs revealed more potent antiproliferative effect against GASTRIC CANCER cells compared with aptNCL alone (P=0.0001). It was found that the aptNCL-let-7d CONJUGATE efficiently carried let-7d into the cancer cells. Also, it appears that in the setting of aptNCL-let-7d CONJUGATE, let-7d and aptNCL moieties could cooperate and synergistically exhibit the antiproliferative effect on cancer cells.

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APA: Copy

DAEI, PUYAN, RAMEZANPOUR, MAHSA, KHANAKI, KOROSH, TABARZAD, MARYAM, NIKOKAR, IRAJ, HEDAYATI CH., MOJTABA, & ELMI, ALI. (2018). APTAMER-BASED TARGETED DELIVERY OF MIRNA LET-7D TO GASTRIC CANCER CELLS AS A NOVEL ANTI-TUMOR THERAPEUTIC AGENT. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 17(4), 1537-1549. SID. https://sid.ir/paper/288900/en

Vancouver: Copy

DAEI PUYAN, RAMEZANPOUR MAHSA, KHANAKI KOROSH, TABARZAD MARYAM, NIKOKAR IRAJ, HEDAYATI CH. MOJTABA, ELMI ALI. APTAMER-BASED TARGETED DELIVERY OF MIRNA LET-7D TO GASTRIC CANCER CELLS AS A NOVEL ANTI-TUMOR THERAPEUTIC AGENT. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2018;17(4):1537-1549. Available from: https://sid.ir/paper/288900/en

IEEE: Copy

PUYAN DAEI, MAHSA RAMEZANPOUR, KOROSH KHANAKI, MARYAM TABARZAD, IRAJ NIKOKAR, MOJTABA HEDAYATI CH., and ALI ELMI, “APTAMER-BASED TARGETED DELIVERY OF MIRNA LET-7D TO GASTRIC CANCER CELLS AS A NOVEL ANTI-TUMOR THERAPEUTIC AGENT,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 17, no. 4, pp. 1537–1549, 2018, [Online]. Available: https://sid.ir/paper/288900/en

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