Biomedical Engineering Reference
In-Depth Information
gliomas. Bernardi et al. [185] evaluated the efficacy of immunonanoshells
in vitro against both medulloblastoma and malignant glioma cell lines. In
this study, the authors, using gold-silica nanoshells, coated with an anti-
body against human epidermal growth factor receptor (HER2) to target
medulloblastoma cells, showed cell death in the HER2-overexpressing
medulloblastoma cell lines after exposure to laser light. The same authors
conjugated gold-silica nanoshells to an antibody specific to interleukin-13
receptor alpha 2 (IL-13Ra2), strongly expressed in gliomas, demonstrating
that these immunonanoshells are capable of leading to cell death in U373
and U87 malignant glioma cell lines. Convection-enhanced delivery (CED)
techniques were developed to address the diffusion limited penetration of
agents directly delivered to the brain. This strategy has been used to deliver
proteins and small particles, including liposomes and polymeric nanopar-
ticles into the brain. CED provides penetration through a large volume of
brain tissue but it is limited by unpredictable drug distribution and poten-
tially high intracranial pressures. Combining polymeric controlled release
with CED could improve the drug distribution limitations of implantable
wafers while also offering spatiotemporal distribution control that is lacking
from CED. Poly(lactic-co-glycolic acid) (PLGA) is capable of encapsulating
and releasing a variety of agents, including chemotherapy drugs, for long pe-
riods of time. The authors evaluated the efficacy of CED of surface-modified,
drug-loaded, PLGA NPs to treat intracranial glioma using the topoisomerase
I inhibitor camptothecin (CPT). CPT is an attractive drug for delivery by
controlled release because it has known anticancer activity, but is limited
by low solubility and serious systemic toxicity. The NPs were shown to be
effective both in culture and in vivo, with a statistically significant survival
benefit observed in all animals treated [248].
CED of iron oxide NPs in a
mouse glioma model results in MRI contrast of the nanoparticles and effec-
tive intratumoral and peritumoral distribution of nanoparticles in the brain.
A significant therapeutic effect was found after CED of both IONPs and
EGFRvIIIAb-IONPs in mice. Dispersion of the NPs over days, after the
infusion has finished, may potentially target infiltrating tumor cells outside
the tumor mass that are potentially responsible for tumor recurrence and
the demise of patients. Use of bioconjugated magnetic NPs may permit the
advancement of CED in the treatment of malignant gliomas due to their
sensitive imaging qualities on standard T2 weighted MRI and therapeutic
effects [249]. Cyclo-oxygenase (COX)-2 is the key enzyme in arachidonic
acid metabolism resulting in prostaglandin production, and is induced by
several factors, such as growth factors, cytokines, and tumor promoters. In
particular, COX-2 expression and prostaglandin production are associated
with tumorigenesis and tumor progression. Celecoxib, a selective COX-2 in-
hibitor, has been reported to mediate growth inhibitory effects and to induce
apoptosis in various cancer cell lines. PLGA nanoparticles incorporating
celecoxib were prepared for antitumor drug delivery. PLGA nanoparticles
