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Poster display - Cocktail

1237 - CXCR4 antagonist mediated targeting of cancer cells using nanoparticles

Date

24 Nov 2018

Session

Poster display - Cocktail

Presenters

Shiba Ansari

Citation

Annals of Oncology (2018) 29 (suppl_9): ix23-ix27. 10.1093/annonc/mdy430

Authors

S. Ansari1, M. Mudassir1, B. Vijayalekshmi2, P. Chattopadhyay1

Author affiliations

  • 1 Department Of Biochemistry, All India Institute of Medical Sciences, 110029 - Delhi/IN
  • 2 Department Of Biochemistry, Christian Medical College, 632004 - Vellore/IN
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Resources

Abstract 1237

Background

Chemokine receptor, CXCR4 is overexpressed in cancer stem cells and mediates tumor progression by controlling cancer cell survival, proliferation and migration. So, development of targeted therapeutics using CXCR4 ligands offers a promising approach for cancer treatment. Studies have reported DV1 peptide ligand (derived from viral macrophage inflammatory protein-II) to possess high affinity and antagonistic activity for chemokine receptor CXCR4. PLGA {Poly (lactide-co-glycolide)} based nanoparticles (NP) can be used for targeted delivery of therapeutics owing to their biocompatibility, efficient cellular uptake, rapid lysosomal escape and sustained drug release properties. Therefore, we aimed to target CXCR4 receptors using Avidin-PLGA nanoparticles tagged with biotinylated DV1-peptide ligand in glioblastoma cell lines.

Methods

Avidin-PLGA nanoparticles were prepared by double emulsion solvent evaporation technique and size characterization done by Transmission Electron Microscope. Fluorescein isothiocyanate (FITC) was incorporated inside the nanoparticles to facilitate cellular uptake analysis of these nanoparticles by confocal microscope. Surface functionality of nanoparticles for avidin groups was also ascertained by confocal microscope. For specific targeting of CXCR4 receptors, Targeted nanoparticles (Peptide-Avidin PLGA NP) were prepared by tagging biotinylated DV1 peptide onto the surface of Avidin-PLGA nanoparticles. Untagged nanoparticles were used as Control nanoparticles (Avidin-PLGA NP). U87MG (CXCR4 positive) and Neuro-2a (CXCR4 negative) cell lines were taken as test and control cells respectively. Analysis was done by confocal microscope and Nikon NIS-elements BR software.

Results

Experimental results revealed significantly enhanced uptake of Targeted nanoparticles in U87MG cells as compared to Neuro-2a cells thereby confirming specificity of Targeted nanoparticles for CXCR4 receptors.

Conclusions

Our results suggest that Avidin-PLGA NP tagged with DV1 peptide can be used for targeted therapy to CXCR4 expressing cells. This targeted therapy has potential clinical application in treatment of various cancer and other diseases like HIV.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

All India Institute of Medical Sciences.

Funding

Department of Biotechnology (DBT), India.

Disclosure

All authors have declared no conflicts of interest.

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