Details

Autor(en) / Beteiligte

• Lizoňová, Denisa
• Majerská, Monika
• Král, Vlastimil
• Pechar, Michal
• Pola, Robert
• Kovář, Marek
• Štěpánek, František

Titel

Antibody-pHPMA functionalised fluorescent silica nanoparticles for colorectal carcinoma targeting

Ist Teil von

• RSC advances, 2018-01, Vol.8 (39), p.21679-21689

Ort / Verlag

England: Royal Society of Chemistry

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The systemic application of highly potent drugs such as cytostatics poses the risks of side effects, which could be reduced by using a carrier system able to specifically deliver the encapsulated drug to the target tissue. Essential components of a nanoparticle-based drug delivery system include the drug carrier itself, a targeting moiety, and a surface coating that minimizes recognition by the immune system. The present work reports on the preparation, characterization and testing of a new delivery system consisting of fluorescent silica nanoparticles functionalised with a non-immunogenic stealth polymer poly( -(2-hydroxypropyl)methacrylamide) (pHPMA) and a monoclonal antibody IgG M75 that specifically binds to Carbonic Anhydrase IX (CA IX). CA IX is a promising therapeutic target, as it is a hallmark of several hypoxic tumours including colorectal carcinoma. Uniquely in this work, the monoclonal antibody was covalently coupled to the surface of fluorescently labelled silica nanoparticles a multivalent amino-reactive co-polymer rather than a traditional bivalent linker. The pHPMA-M75 functionalised SiO nanoparticles exhibited excellent colloidal stability in physiological media. Their characterisation by flow cytometry proved a highly specific interaction with colorectal carcinoma cells HT-29. study on athymic NU/NU nude mice revealed that the SiO -pHPMA-M75 nanoparticles are capable of circulating in the blood after intravenous administration and accumulate in the tumour at tenfold higher concentration than nanoparticles without specific targeting, with a considerably longer retention time. Additionally, it was found that by reducing the dose administered , the selectivity of the nanoparticle biodistribution could be further enhanced in favour of the tumour.