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 in vivo 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. In vitro, in vivo, and ex vivo 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.
Assessing the in vivo targeting efficiency of multifunctional nanoconstructs bearing antibody-derived ligands / L. Fiandra, S. Mazzucchelli, C. De Palma, M. Colombo, R. Allevi, S. Sommaruga, E. Clementi, M. Bellini, D. Prosperi, F. Corsi. - In: ACS NANO. - ISSN 1936-0851. - 7:7(2013 Jul 23), pp. 6092-6102.
|Titolo:||Assessing the in vivo targeting efficiency of multifunctional nanoconstructs bearing antibody-derived ligands|
FIANDRA, LUISA (Primo)
MAZZUCCHELLI, SERENA (Secondo)
CORSI, FABIO RUGGERO MARIA (Ultimo)
|Parole Chiave:||antibodies ; cell membrane ; humans ; MCF-7 cells ; materials testing ; nanocapsules|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/18 - Chirurgia Generale
|Data di pubblicazione:||23-lug-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/nn4018922|
|Appare nelle tipologie:||01 - Articolo su periodico|