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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.

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.
AuthorsSeyedeh Alia Moosavian, Khalil Abnous, Javad Akhtari, Leila Arabi, Ali Gholamzade Dewin, Mahmoudreza Jafari
JournalArtificial cells, nanomedicine, and biotechnology (Artif Cells Nanomed Biotechnol) Vol. 46 Issue 8 Pg. 2054-2065 (Dec 2018) ISSN: 2169-141X [Electronic] England
PMID29205059 (Publication Type: Journal Article)
Chemical References
  • 5TR1 aptamer
  • Aptamers, Nucleotide
  • Liposomes
  • Mucin-1
  • muc1 protein, mouse
  • Doxorubicin
Topics
  • Animals
  • Aptamers, Nucleotide (chemistry, pharmacology)
  • CHO Cells
  • Colonic Neoplasms (drug therapy, metabolism, pathology)
  • Cricetulus
  • Doxorubicin (chemistry, pharmacology)
  • Female
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Mucin-1
  • Neoplasms, Experimental (drug therapy, metabolism, pathology)

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