Zinc-phosphate nanoparticles with reversibly attached TNF-[alpha] analogs: an interesting concept for potential use in active immunotherapy

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology 2011-07, Vol.13 (7), p.3019
• Main Authors: Hribar, Gorazd, Nidarsic, Andrej, Bele, Marjan, Maver, Uros, Caserman, Simon, Gaberscek, Miran, Gaberc-porekar, Vladka
• Format: Article
• Language: English
• Subjects: Immunotherapy; Nanoparticles; Zinc
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-010-0199-5

The authors' intention was to prepare nanometer-sized zinc-phosphate nanoparticles that would be capable of binding histidine-rich TNF-α analogs onto their surface via a coordinative bond. Zinc-phosphate nanoparticles with a size of around 60 nm were prepared by a wet precipitation method and characterized using SEM, EDX, XRD, and DLS. First, BSA was bound as a testing protein, afterward two TNF-α analogs with decreased activity were bound to the described nanoparticles. The efficiency of binding and the existence of coordinative bond were confirmed with SDS-PAGE analysis. During binding, particle storage, and release experiments, the prepared TNF-α analogs retained their biological activity--hence the epitopes necessary for formation of antibodies stayed intact. The particle size did not change within a period of 2 weeks. No significant agglomeration was observed, the particles could be quickly dispersed in ultrasound. The present nanoparticles and the general approach of coordinative binding are widely applicable for natural and engineered histidine-rich proteins. The nanoparticles bearing appropriate TNF-α analogs could also be potentially used for active immunotherapy to tackle the chronic inflammatory diseases associated with pathogenically elevated levels of TNF-α.[PUBLICATION ABSTRACT]