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(17c) Stealth Nanoparticles for Tumor Targeting: in vivo and in vitro Characterization (Invited)

Authors: 
Lizonova, D., University of Chemistry and Technology
Stepanek, F., University of Chemistry and Technology
Kral, V., Department of Chemical Engineering, University of Chemistry and Technology
Pola, R., Academy of Sciences of the Czech Republic, v. v. i.
Pechar, M., Academy of Sciences of the Czech Republic, v. v. i.
Kovar, M., Academy of Sciences of the Czech Republic, v. v. i
Silica nanoparticles with proper surface modifications can sufficiently mimic chemical robot - an intelligent particle which can “find, visualize and cure” the tumor and thus might be used in the targeted drug delivery research. The successful tumor targeting is limited by not only the targeting technique and particle size but also the invisibility for the immune system (”stealth”), which goes hand in hand with the ability of nanoparticles to circulate in the bloodstream for more than few minutes. The presented work focuses on the preparation, characterization and in vivotesting of fluorescently labeled silica nanoparticles modified with stealth poly (N-(2-hydroxypropyl) methacrylamide) (pHPMA) and monoclonal antibody IgG M75 against Carbonic Anhydrase IX (CA IX, targeting to the hypoxic tumors like colorectal adenocarcinoma).

Fluorescently labeled (fluorescein isothiocyanate) silica nanoparticles with mean diameter of ≈170 nm and zeta potential between -15 and -20 mV exhibited great colloidal stability in buffers and physiological media when modified with pHPMA. The amount of pHPMA and IgG M75 on the nanoparticle surface was evaluated via amino acid analysis with resulting 3.6 w.% and 1.0 w.%, respectively. Further in vitro characterization employing flow cytometry and two different cell lines (HT-29: expresses CA IX; DLD-1: does not express CA IX; negative control) showed specific interaction of IgG M75-modified nanoparticles with HT‑29 cell line while no nonspecific interactions were detected. Finally, the in vivo study on Nu-Nu nude mice with tumors grown from HT-29 cell line revealed that nanoparticles bearing IgG M75 antibody can accumulate in the tumor in tenfold higher concentration and are retained considerably longer than nanoparticles without specific targeting. Furthermore, the nanoparticles were detected in the blood even after 60 minutes after the intravenous administration, which might be contributed to the stealth pHPMA coverage, providing the sufficient contact with the organism and thus increases the possibility to reach the target.

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