Biomedical Engineering Reference
In-Depth Information
7.
Experimental studies
Nanoparticle systems, can represent ideal devices for delivery of specific com-
pounds to brain tumors across the BBB [4-5, 241-242]. Nanotechnology
and nanomedicine have been utilized to perform new therapeutic intracere-
bral drug delivery systems, and to develop treatments for various diseases
and disorders. By using nanotechnology in drug design and delivery, it will
be possible to deliver the drug to the targeted tissue and cells across the
BBB, to release the drug at the controlled rate, and to be able to escape from
degradation processes. Solid tumors require therapies to actively penetrate
deeply into the tumor in order to affect a large proportion of cancer cells.
Nanotechnology provides a unique advantage in glioma therapy since the
size scale is on the order of the proteins used for cell function. The size
and shape of NPs can be tuned to exert a desired therapeutic response on a
specific target.
Antiangiogenic approaches have been extensively exploited to provide
a rationally designed therapy for the treatment of malignant gliomas. The
brain tumor endothelium, with characteristics of high proliferation, high
permeability, and high expression of proangiogenic factors, is a particularly
appealing therapeutic target for this strategy [243-245]. Antiangiogenic
approaches in glioma therapy have been strongly directed against a VEGF
pathway. In an in vivo murine model, created by implantation of U-87 MG
malignant glioma cells in mice, Im et al. [246] demonstrated the suppression
of ability of glioma cells to form tumors in mice. This result was obtained
after transfection of antisense VEGF cDNA, in an antisense orienta-
tion through the recombinant adenoviral vector Ad5CMV-alphaVEGF.
Infection of U-87 MG malignant glioma cells resulted in the reduction
of the level of the endogenous VEGF mRNA, and in reduced production
of the VEGF targeted secretory form. Agemy et al. [247] have proposed a
multifunctional theranostic NP in which the CGKRK peptide provides the
targeting function that takes the NPs to tumor vascular cells and into their
mitochondria. The NP uses the mitochondria-targeted
D
[KLAKLAK]
2
peptide as the drug and iron oxide, as a diagnostic component for MRI.
In addition, the NP was combined with the tumor-penetrating peptide
iRGD which enhances the NP penetration into the extravascular tumor
tissue. Systemic treatment of GBM-bearing mice with this compound
eradicated most tumors in one GBM mouse model, and significantly de-
layed tumor development in another. An important molecular target used
to selectively detect glioma cells is IL-13, based on up-regulated expression
of IL-13a2 on the surface of GBM cells. In a recent study, Madhankumar
et al. [187] showed the improvement of internalization of doxorubicin-
loaded nanoliposomes targeted with conjugated IL-13, as compared to non-
targeted nanoliposomes in U251 glioma cells. In an in vivo animal model,
the authors demonstrated growth inhibition of subcutaneously implanted
