Oncotarget

Research Papers:

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study

Weirong Kang, Darren Svirskis, Vijayalekshmi Sarojini, Ailsa L. McGregor, Joseph Bevitt, Zimei Wu _

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Oncotarget. 2017; 8:36614-36627. https://doi.org/10.18632/oncotarget.16625

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Abstract

Weirong Kang1, Darren Svirskis1, Vijayalekshmi Sarojini2, Ailsa L. McGregor1, Joseph Bevitt3 and Zimei Wu1

1School of Pharmacy, University of Auckland, Auckland 1142, New Zealand

2School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand

3Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organization, Sydney 2232, Australia

Correspondence to:

Zimei Wu, email: z.wu@auckland.ac.nz

Keywords: boron neutron capture therapy (BNCT), dual-targeting drug delivery, glioblastomas, Integrin αv and β3, cyclic RGD peptides

Received: November 09, 2016     Accepted: March 01, 2017     Published: March 28, 2017

ABSTRACT

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma.

Author Information

Weirong Kang

Darren Svirskis

Vijayalekshmi Sarojini

Ailsa L. McGregor

Joseph Bevitt

Zimei Wu
Primary Contact  _


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