Antibody-Functionalized Inorganic NPs: Mimicking Nature for Targeted Diagnosis and Therapy - Bioinspired Approaches for Human-Centric Technologies - page 18

variant nanocomplexes were retained for longer time and the fluorescent signal did
not decrease over time, as instead occurred with the NP-TZ. This is likely due to a
better and prompter interaction of the smaller nanostructures with the membrane
receptor, thus resulting in a more efficient tumor targeting. The authors also
claimed that the large size of the whole antibody may affect the stability of the
bionanocomplex which tends to form aggregates, thus finally reducing the ability to
bind the target.
In a previous work from the same group, NP-TZ were injected in tumor-bearing
mice: the accumulation at the tumor site and the biodistribution were evaluated by
epifluorescence, MRI, and postmortem TEM and histological analysis (Corsi
et al. 2011 ). Remarkably, immunohistochemical analysis of extracted tumor tissues
showed that NP-TZ saturated HER2 molecules on the surface, thus suggesting their
exploitation as adjuvant immunotherapeutic agent in cancer treatment.
Cancer adjuvant therapy with monoclonal antibodies has been already
established for several malignancies, and their combination with inorganic nano-
particles can undoubtedly enhance the potential use, enabling simultaneously
targeting, imaging, and therapy. This is the encouraging perspective provided by
the group of Mao, which developed iron oxide nanoparticles conjugated to an
EGFRvIII deletion mutant antibody for targeting glioblastoma (Hadjipanayis
et al. 2010 ). This variant form of the receptor is expressed in malignant gliomas
but not in normal cells, thus making targeting highly selective. In order to facilitate
BBB penetration, convection-enhanced delivery (CED) was applied. The results
provided evidence that, once in the brain, the anti-EGFRvIII NP not only targeted
cancer cells and allowed MRI contrast enhancement but most significantly elicited
tumor reduction by means of EGFR signaling interruption. Indeed, the authors
supposed that binding of the NP to the EGF receptor results in reduced phosphory-
lation of the downstream proteins and thus in apoptosis induction.
In a very recent paper, tumor regression was obtained through a more complex
and promising approach, i.e., through combined magnetic hyperthermia and che-
motherapy (Li et al. 2013 ). A multifunctional nanostructure consisting of a mag-
netite core loaded with the anticancer drug 5-fluorouracil (5-FU) and functionalized
with anti-HER2 antibody was developed. The nanoparticles were injected either
intratumorally or in the tail vein in a bladder cancer mouse model. In both cases, the
combination of hyperthermia and synchronized local chemotherapy was more
effective in cancer regression than the individual treatment. Although these results
are extremely encouraging, it is worth to mention that the radio-frequency para-
meters used in this work (1.3 MHz radio frequencies and 33 kA/mmagnetic field) to
activate the thermal response were out of the clinical relevance range for patients.
For application on humans, lower radio frequencies (within the range 80-200 KHz
and maximum 30 KA/m) need to be used to prevent deleterious side effects, and
therefore new nanoparticle formulations with optimal heating performance have to
be prepared. Almost all the other in vivo studies performed with Ab-conjugated
NPs were focused to cancer targeting, to analyze nanoparticle biodistribution and in
some cases to assess cancer imaging ability, as reported in Table 1.1 .