Antibody-Functionalized Inorganic NPs: Mimicking Nature for Targeted Diagnosis and Therapy - Bioinspired Approaches for Human-Centric Technologies - page 17

In this context, monoclonal antibodies can bring significant benefits: the devel-
opment and the engineering of antibodies that target specifically tumor biomarkers,
i.e., those receptors or biomolecules which are overexpressed or expressed only at
the surface of tumor cells, can greatly enhance drug delivery efficiency and thus
therapeutic effectiveness. As already described in the previous sections, also
inorganic nanoparticles contribute to the technological revolution that can improve
cancer diagnosis and therapy. Therefore, it is not surprising that most of the recent
in vivo studies performed with Ab-conjugated nanoparticles aim to evaluate their
functionality and most specifically their diagnostic/therapeutic potential in rodent
tumor models. In particular, these works are focused to achieve and demonstrate the
three following objectives, either independently or simultaneously: (1) the targeting
efficiency, (2) the diagnostic relevance, and (3) the therapeutic effect of the
Ab-derived nanocomplexes.
Tumor active targeting is not straightforward and can be affected by several
factors, such as the type of biomarker to target (i.e., its tumor-related specificity and
the level of expression at the tumor site), the binding ability of the NP-bound
antibody, the size and the stability of the nanocomplex, the type of tumor and its
location, and the administration route. An interesting study on the targeting is the
work of Glazer and co-workers in which gold nanoparticles were functionalized
with either cetuximab or PAM4 antibodies (Glazer et al. 2010 ). The first is a
recombinant biomolecule against the epidermal growth factor receptor (EGFR),
which is overexpressed in several malignancies and is present even on healthy cells,
while the second is an antibody against a specific pancreatic cancer antigen
(MUC1). Mice bearing a xenograft pancreatic tumor were first injected with the
Ab-NP and then exposed to radio frequencies (RF, 13.56 MHz, 600 W generator
power for 10 min with an air gap of 10 cm) in order to trigger Au-mediated tumor
thermal ablation. Subsequent to nanoparticles injection, RF exposure occurred one
time per week. After 6 weeks of treatment, animals were sacrificed. The measure-
ments of tumor volume showed that cetuximab-conjugated Au-NPs were more
effective in tumor regression than PAM-conjugated counterparts, likely because
EGFR, despite its low tumor specificity, is expressed on tumor cells at higher
amounts than MUC1, thus enabling better targeting.
Interesting in vivo studies have been carried out to evaluate the effect of the
tumor binding as a function of the antibody-nanoparticle molecular weights; in
some cases, the whole antibody was attached to the NP and compared to the use of
fragments of the same antibody. In a very recent study, for instance, the human
epidermal growth factor receptor (HER2) was selected as biological target, and
three anti-HER2 antibody variants were conjugated to iron oxide nanoparticles
bearing a fluorescent moiety (Fiandra et al. 2013 ). In detail, a whole recombinant
antibody, trastuzumab (TZ), a half-chain antibody (HC), and a single-chain variable
fragment (scFv), respectively, were bound to the NPs in order to evaluate the effect
of the antibody size on the tumor targeting ability of the whole nanocomplex. The
data collected showed that NP-HC and NP-scFv were endocytosed by HER2-
expressing cells faster than NP-TZ. Moreover, measurement of the NP retention
time at the tumor site in breast cancer models confirmed that the two antibody