Optimization and radiolabeling of ultrasmall upconverting nanoparticles for multimodal cancer imaging

In recent years, multimodal imaging has obtained increasing attention since it is an attractive strategy to combine the advantages of different imaging modalities, aiming to enhance the efficiency and sensitivity of disease diagnosis and imaging of treatment progress. In this context, nanoparticles come to the fore due to their diversity and versatility. Depending on the material used, nanoparticles themselves can already constitute an imaging probe because of magnetic and/or fluorescence properties which enable magnetic resonance (MR) or optical imaging. In addition, they offer the opportunity for multiple functionalization to introduce additional labels and biospecific molecules on their surface. Nanoparticles of particular interest are the so-called “upconverting nanophosphors” (UCNPs). With their exceptional ability to convert near-infrared to visible light (upconversion), these inorganic lanthanide-doped nanoparticles are very attractive for biomedical applications. Their excitation in an optical transparency window (the “biological window” between 700-1000 nm) enables deep penetration into tissue, as well as high contrast related to minimum autofluorescence in this spectral range. Furthermore, these materials have shown no inherent toxicity effects in both in vitro and in vivo studies. Known syntheses of UCNPs generate mainly hydrophobic particles. However, there are several possibilities to achieve biocompatibility by applying different coating strategies [1]. Here, we discuss the synthesis and photophysical properties of ultrasmall (<10 nm) UCNPs based on a host lattice of nanocrystalline NaYF₄ doped with Yb³⁺ as a sensitizer, as well as Er³⁺ or Tm³⁺ as emitter ions with an excitation wavelength at 980 nm. Additionally, by insertion of Nd³⁺ as a primary sensitizer, the excitation wavelength can be changed to 795 nm, resulting in deeper tissue penetration and lower heating effects associated with water absorption in the range of 1000 nm. Furthermore, by using an active shell strategy, quenching effects can be reduced. The most appropriate UCNPs were coated with amphiphilic polymers in order to achieve highly colloidally-stable, water-dispersible systems suitable for biomedical applications. In this way, further functionalization with targeting vector molecules and the introduction of bifunctional chelators is possible. By way of demonstration, a dipicolyl derivative of 1,4,7-triazacyclononane has been coupled as a radiocopper chelator to allow for ⁶⁴Cu-based positron emission tomography [2].

References
1. G. Chen, H. Qiu, P. N. Prasad and X. Chen, Chem. Rev. (2014), DOI: 10.1021/cr400425h.

2. K. Pombo-García, K. Zarschler, J. A. Barreto, J. Hesse, L. Spiccia, B. Graham and H. Stephan, RSC Adv. 3, 22443 (2013).