Multifunctionalization of Ultrasmall Upconverting Nanoparticles for Multimodal Cancer Imaging

The design of multimodal imaging systems for disease diagnosis and imaging of treatment progress has been receiving increasing attention in recent years. The combination of two or more imaging modalities allows the limitations of each method to be overcome and ultimately provides the ability to enhance the sensitivity and efficiency of diagnosis. A promising platform for the development of targeted imaging agents are ultrasmall nanoparticles (< 10 nm) as they offer the opportunity for multifunctionalization of the particle surface with different labels and biospecific molecules. Additionally, the nanomaterials themselves can exhibit magnetic and/or fluorescence properties that enable their applications as magnetic resonance (MR) or optical imaging probes. So-called “upconverting nanoparticles” (UCNPs) represent an intriguing class of optical imaging agents, especially for biomedical applications. The attraction of these nanomaterials derives from their capacity for excitation in the biologically transparent window (700-1000 nm), exceptional ability to convert near infrared radiation into visible light (upconversion), and capability for deep tissue, high contrast imaging related to minimum autofluorescence in this spectral range [1]. Here, we discuss the design, synthesis and surface modification of ultrasmall (<10 nm) UCNPs with an excitation wavelength of 795 nm, which are based on a host lattice of crystalline NaYF₄ doped with Nd³⁺ and Yb³⁺ as sensitizers, and Er³⁺ or Tm³⁺ as emitter ions. Established strategies for producing UCNPs yield mainly hydrophobic particles[1]. We report the conversion of these into water-soluble, colloidally-stable, biocompatible and multi-functionalized platforms using polymer coating and ligand exchange strategies, and the influence of the coating on the UCNPs’ photophysical properties. As a proof-of-concept, a radiocopper (⁶⁴Cu) chelator has been coupled to produce a UCNP-based bimodal imaging agent for in vitro and PET (positron emission tomography) studies.

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