Article

Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(beta-L-malic acid).

Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Journal of Controlled Release (impact factor: 5.73). 11/2007; 122(3):356-63. DOI:10.1016/j.jconrel.2007.05.032
Source: PubMed

ABSTRACT Tumor-specific targeting using achievements of nanotechnology is a mainstay of increasing efficacy of anti-tumor drugs. To improve drug targeting we covalently conjugated for the first time two different monoclonal antibodies, an anti-mouse transferrin receptor antibody and a mouse autoimmune anti-nucleosome antibody 2C5, onto the drug delivery nanoplatform, poly(beta-L-malic acid). The active anti-tumor drug components attached to the same carrier molecule were antisense oligonucleotides to vascular protein laminin-8. The resulting drug, a new Polycefin variant, was administered intravenously into glioma-bearing xenogeneic animals. The drug delivery system was targeted across mouse endothelial system by the anti-mouse transferring receptor antibody and to the tumor cell surface by the anti-nucleosome antibody 2C5. The targeting efficacies of the Polycefin variants bearing either two antibodies or each single antibody were compared in vitro and in vivo. ELISA confirmed the co-existence of two antibodies on the same nanoplatform molecule and their functional activities. Fluorescence imaging analysis after 24 h of intravenous injection demonstrated significantly higher tumor accumulation of Polycefin variants with the tandem configuration of antibodies than with single antibodies. The results suggest improved efficacy for tandem configuration of antibodies than for single configurations carried by a drug delivery vehicle.

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Keywords

active anti-tumor drug components
 
anti-mouse
 
anti-mouse transferrin receptor antibody
 
anti-nucleosome antibody 2C5
 
drug delivery nanoplatform
 
drug delivery system
 
drug delivery vehicle
 
Fluorescence imaging analysis
 
functional activities
 
glioma-bearing xenogeneic animals
 
higher tumor accumulation
 
mouse autoimmune anti-nucleosome antibody 2C5
 
mouse endothelial system
 
nanoplatform molecule
 
new Polycefin variant
 
poly(beta-L-malic acid)
 
Polycefin variants bearing
 
resulting drug
 
tumor cell surface
 
vascular protein laminin-8