Ultrasmall nanomaterials for biomedical applications

The field of nanomedicine offers excellent prospects for the development of new non-invasive strategies for the diagnosis and therapy of cancer [1, 2]. A major advantage of nanomaterials (NMs) is their potential to be used as non-invasive diagnostic tools. By combining multiple modalities into a single probe, higher sensitivity can be achieved, leading to deeper insights into different in vitro and in vivo processes. Despite the significant progress that has been made in the field of NMbased cancer diagnostics, our overall understanding of their pharmacokinetics (adsorption, uptake, distribution, metabolism and excretion) is still limited. Detailed investigations of the physicochemical properties and physiological behavior of NMs in biological environments are required to be better able to understand, predict and control their biodistribution.
We are aiming to develop targeted nanomaterials capable of imaging cancer by a combination of positron emission tomography PET, fluorescence optical imaging (OI) and/or magnetic resonance imaging (MRI) to provide a deeper understanding of their interactions in vitro and in in vivo. For the development of any functional nanomaterial to be applied for cancer imaging, it is of utmost importance to evade capture by the mononuclear phagocyte system and to circulate in vivo until reaching the target. It is now well recognized that ultrasmall (< 6 nm), renally-excretable particles are the most appropriate from this point of view, provided that they can be coupled to an efficient targeting vector.
Prototypes of highly-defined narrow-sized NPs have been developed and characterized, e.g. 2 - 4 nm-sized silicon NPs with reactive surface moieties, such as amino and carboxylic acid groups. Ultrasmall superparamagnetic iron oxide (USPIOs), upconverting nanophosphors and dendritic polyglycerol derivatives (< 10 nm) are also available as defined platforms. New assembly strategies, resulting in well-defined surface-attached radiochelates, fluorophores and targeting vectors will be presented. This includes in particular the engineering of zwitterionic-coated “stealth” NPs, leaving only targeting groups directly exposed to the surrounding biological milieu. [3] A small camelid single-domain antibody (sdAb) was chosen as targeting vector of the epidermal growth factor receptor (EGFR) which is overexpressed in a variety of solid tumors. [4]

References:

[1] Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5 (2005) 161-71.
[2] Kim, B. Y.; Rutka, J. T.; Chan, W. C. Nanomedicine. N. Engl. J. Med. 363 (2010) 2434-43.
[3] Pombo García, K.; Zarschler, K.; Barbaro, L.; Barreto, J. A.; O'Malley, W.; Spiccia, L.; Stephan, H.; Graham, B. Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent advances in countering
biomolecular corona formation and uptake by the mononuclear phagocyte system. Small 10 (2014) 2516-2529.
[4] Zarschler, K.; Prapainop, K.; Mahon, E.; Rocks, L.; Kelly, P. M.; Bramini, M.; Stephan, H.; Dawson, K. A. Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.
Nanoscale 6 (2014) 6046-6056.