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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1007/11531746_4

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1573-904X

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StarShaped Tetraspermine Enhances Cellular Uptake

Authors: Vidula Kolhatkar Hiren Khambati Asawari Lote Peter Shanine Thomas Insley Soumyo Sen Gnanasekar Munirathinam Petr Král Rohit Kolhatkar
Publish Date: 2014/08/05
Volume: 32, Issue: 1, Pages: 196-210
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Abstract

An oligonucleotide termed ‘Toligo’ having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers We have demonstrated that Toligo can induce apoptosis in androgen independent prostate cancer cell line DU145 In this report we evaluate the use of starshaped tetraspermine SSTS for delivery of ToligoSSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU145 cells was compared with spermine and branched polyethyleneimine bPEI Atomistic molecular dynamic MD simulations were conducted to understand binding and complexation of spermine and SSTS with Toligo Complexation was also determined using gel electrophoresis and SYBR gold assay Complexes were characterized for size cellular uptake and antiproliferative effectSSTS exhibited significantly lower toxicity than spermine and bPEI Its affinity towards Toligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes TONPs with Toligo TONPs facilitated cellular uptake and nuclear accumulation of Toligo and their cytotoxic potential was observed at concentration several folds lower than that required for Toligo alone

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