5TR1 aptamer-PEGylated liposomal doxorubicin enhances cellular uptake and suppresses tumour growth by targeting MUC1 on the surface of cancer cells

Moosavian, S. A. and Abnous, K. and Akhtari, J. and Arabi, L. and Gholamzade Dewin, A. and Jafari, M. (2018) 5TR1 aptamer-PEGylated liposomal doxorubicin enhances cellular uptake and suppresses tumour growth by targeting MUC1 on the surface of cancer cells. Artificial Cells, Nanomedicine and Biotechnology, 46 (8). pp. 2054-2065.

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5TR1 aptamer-PEGylated liposomal doxorubicin enhances cellular uptake and suppresses tumour growth by targeting MUC1 on the surface of cancer cells.pdf

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Abstract

Employing targeting ligands with high affinity to tumour receptors is an important strategy to increase treatment efficacy. The use of aptamers as targeting agent is increasingly prevalent in drug delivery systems. Mucin1 (MUC1) is a glycoprotein that is over-expressed on the surface of several cancer cells and plays an important role in metastasis and invasion. 5TR1-aptamer is a DNA aptamer, which targets MUC1 receptors. The present study investigated the anti-tumour activity and therapeutic effectiveness of 5TR1-aptamer-PEGylated liposomal doxorubicin (PLD) delivery system in C26 tumour-bearing mice. The in vitro experiments demonstrated enhanced cytotoxicity and cellular uptake of PLD at the presence of 5TR1 aptamer into MUC1 + C26 cell line. Biodistribution study indicated that aptamer conjugation increased tumour accumulation of PLDs. Pharmacokinetic analysis showed despite higher clearance rate, selective delivery of doxorubicin to tumour tissue was increased in the 5TR1-Doxil group. In C26-bearing tumour mice, treatment with 5TR1-Doxil exhibited significant deceleration in tumour growth and enhanced survival. The results suggested that 5TR1 aptamer is promising ligand for active targeting which improves therapeutic efficiency of PLD in cancer therapy. © 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Item Type: Article
Additional Information: Cited By :1 Export Date: 16 February 2020 Correspondence Address: Jafari, M.; Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical SciencesIran; email: jafarimr@mums.ac.ir
Uncontrolled Keywords: 5TR1 aptamer active targeting cancer treatment MUC1 PEGylated liposome doxorubicin Cell culture Cells Controlled drug delivery Diseases Ligands Mammals Oncology Tumors Aptamers Doxorubicin Drug delivery system Liposomal doxorubicin Pharmacokinetic analysis Therapeutic efficiency Targeted drug delivery aptamer carboxylic acid macrogol 2000 mucin 1 liposome muc1 protein, mouse aged animal cell animal experiment animal model animal tissue antineoplastic activity area under the curve area under the moment curve Article cancer inhibition cell surface CHO-K1 cell line colon carcinoma conjugation controlled study dispersity drug accumulation drug clearance drug cytotoxicity drug distribution drug formulation drug half life drug protein binding drug release drug targeting drug uptake elimination rate constant female in vitro study liposomal delivery MC-26 cell line mean residence time median survival time micelle mouse nonhuman particle size PEGylation plasma concentration-time curve tumor volume volume of distribution zeta potential animal Bagg albino mouse chemistry CHO cell line colon tumor Cricetulus experimental neoplasm metabolism pathology Animals Aptamers, Nucleotide CHO Cells Colonic Neoplasms Liposomes Mice Mice, Inbred BALB C Mucin-1 Neoplasms, Experimental
Subjects: QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 08 May 2020 15:59
Last Modified: 08 May 2020 15:59
URI: http://eprints.mums.ac.ir/id/eprint/17421

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