10.1021/nn4018922.s001
Luisa Fiandra
Luisa
Fiandra
Serena Mazzucchelli
Serena
Mazzucchelli
Clara De Palma
Clara De
Palma
Miriam Colombo
Miriam
Colombo
Raffaele Allevi
Raffaele
Allevi
Silvia Sommaruga
Silvia
Sommaruga
Emilio Clementi
Emilio
Clementi
Michela Bellini
Michela
Bellini
Davide Prosperi
Davide
Prosperi
Fabio Corsi
Fabio
Corsi
Assessing the <i>In Vivo</i> Targeting Efficiency of Multifunctional Nanoconstructs Bearing Antibody-Derived Ligands
American Chemical Society
2013
surface bioligand
intracellular fate
scFv fragments
HC
MNP
HER 2 receptor
efficiency
model antibody
breast cancer cells
breast cancer detection
MCF 7 cells
target cells
amphiphilic polymer shell
nanoparticle core
Vivo Targeting Efficiency
breast cancer
humanized monocolonal antibody trastuzumab
nanoconstruct
multifunctional nanoparticles
antibody form
vivo localization
physicochemical properties
multifunctional nanoprobes
surface functionalization
TZ
vivo analyses
iron oxide
nanoparticle accumulation
weight variants
2013-07-23 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Assessing_the_i_In_Vivo_i_Targeting_Efficiency_of_Multifunctional_Nanoconstructs_Bearing_Antibody_Derived_Ligands/2393950
A great challenge in nanodiagnostics is the identification of new strategies aimed to optimize the detection of primary breast cancer and metastases by the employment of target-specific nanodevices. At present, controversial proof has been provided on the actual importance of surface functionalization of nanoparticles to improve their <i>in vivo</i> localization at the tumor. In the present paper, we have designed and developed a set of multifunctional nanoprobes, modified with three different variants of a model antibody, that is, the humanized monocolonal antibody trastuzumab (TZ), able to selectively target the HER2 receptor in breast cancer cells. Assuming that nanoparticle accumulation in target cells is strictly related to their physicochemical properties, we performed a comparative study of internalization, trafficking, and metabolism in MCF7 cells of multifunctional nanoparticles (MNP) functionalized with TZ or with alternative lower molecular weight variants of the monoclonal antibody, such as the half-chain (HC) and scFv fragments (scFv). Hence, to estimate to what extent the structure of the surface bioligand affects the targeting efficiency of the nanoconjugate, three cognate nanoconstructs were designed, in which only the antibody form was differentiated while the nanoparticle core was maintained unvaried, consisting of an iron oxide spherical nanocrystal coated with an amphiphilic polymer shell. <i>In vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> analyses of the targeting efficiency and of the intracellular fate of MNP-TZ, MNP-HC, and MNP-scFv suggested that the highly stable MNP-HC is the best candidate for application in breast cancer detection. Our results provided evidence that, in this case, active targeting plays an important role in determining the biological activity of the nanoconstruct.