Biomedical Engineering Reference
In-Depth Information
polybutyl cyanoacrylate NPs, demonstrated a significant decrease in plasma
TGF-b2 and an increase in antitumoral cytotoxicity.
In vitro study of PDT with targeted delivery systems is an alternative
to current adjuvant therapy, and it is characterized by low morbidity and
lack of susceptibility to the development of resistance. PDT involves the
use and delivery of photosensitizers combined with local excitation by the
appropriate wavelength of light, resulting in the production of ROS, which
initiate apoptosis and cytotoxicity in many types of tumors. Moreover,
PDT produces within treated neoplastic tissue microvascular injury leading
to inflammation and hypoxia. This therapeutic approach is more selective
and less toxic than chemotherapy, because the drug is not activated until
the light is delivered. The recent molecular targeting approach selectively
detects cancer cells through molecular-recognition processes such as ligand-
receptor or antibody-antigen interactions. PDT is an interesting approach
for the treatment of malignant gliomas, resulting in a localized treatment
approach with an important improvement in local control of tumors and
a significantly improved survival rate [44]. In a recent study, Wang et al.
[186] have demonstrated prominent photothermal selective damage of 426
targeted glioma cells. Molecular targeting, in this case, has been performed
using carbon nanotubes conjugated with mABs specific to CD133. PDT
using the nanobiohybrid photocatalyst resulted in the destruction of over
80% of A172 glioma cells with high levels of IL13R expression, whereas in
the case of U87 cells characterized by lower antigen presentation, cytotox-
icity at the same conditions reached a plateau of 50% and did not increase
at higher photocatalyst concentrations [139-140]. Moreover, no cytotoxic-
ity was observed for normal human astrocytes (NHA) known to be not
IL13R-expressing [139-140]. Recently Tian et al. [256] showed the feasi-
bility of encapsulating the alkylating agent, temozolomide [(3,4-dihydro-
3-methyl-4-oxoimidazo [5,1-d]-as-tetrazine-8-carboxamide (TMZ)], into
polybutylcyanoacrylate (PBCA) NPs by polymerization. Compared with
TMZ solution, TMZ-PBCA nanoparticles exhibited sustained release in
vitro. Furthermore, based on the pattern of distribution in body organs,
higher concentrations of TMZ can be detected in the brain after binding to
PBCA nanoparticles coated with polysorbate-80, which may be more use-
ful for treating brain tumors. The prepared formulation may also reduce the
toxicity of chemotherapy. Steiniger et al. [257] demonstrated in a murine
glioblastoma model, a statistically significant increase in survival time of
glioblastoma-bearing rats treated with doxorubicin bound to polysorbate-
coated NPs, compared to the control groups treated with other doxorubicin
formulations. More than 20% of the animals showed a long-term remis-
sion and no drug-NP complex neurotoxicity was observed.
In an ongoing
phase I clinical trial, paclitaxel albumin-stabilized NP formulation is be-
ing used in treating advanced cancers such as bladder cancer, and brain and
CNS tumors. The authors demonstrated in a subset of patients a decrease
