Star-shaped tetraspermine enhances cellular uptake and cytotoxicity of T-oligo in prostate cancer cells

Pharm Res. 2015 Jan;32(1):196-210. doi: 10.1007/s11095-014-1455-7. Epub 2014 Aug 5.


Purpose: An oligonucleotide termed 'T-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. We have demonstrated that T-oligo can induce apoptosis in androgen independent prostate cancer cell line DU-145. In this report, we evaluate the use of star-shaped tetraspermine (SSTS) for delivery of T-oligo.

Methods: SSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU-145 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 T-oligo. Complexation was also determined using gel electrophoresis and SYBR gold assay. Complexes were characterized for size, cellular uptake and antiproliferative effect.

Results: SSTS exhibited significantly lower toxicity than spermine and bPEI. Its affinity towards T-oligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes (TONPs) with T-oligo. TONPs facilitated cellular uptake and nuclear accumulation of T-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for T-oligo alone.

Conclusion: SSTS significantly enhanced therapeutic benefits associated with the use of T-oligo and can be developed as a delivery vehicle for its in-vivo therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / chemical synthesis
  • Edetic Acid / chemistry
  • Flow Cytometry
  • Humans
  • Male
  • Molecular Conformation
  • Molecular Dynamics Simulation
  • Nanoparticles / chemistry*
  • Oligonucleotides / administration & dosage
  • Oligonucleotides / pharmacokinetics
  • Oligonucleotides / pharmacology*
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Spermine / analogs & derivatives*
  • Spermine / chemical synthesis
  • Spermine / chemistry


  • Antineoplastic Agents
  • Drug Carriers
  • Oligonucleotides
  • Spermine
  • Edetic Acid