Up-converting inorganic photo-sensitizers for bio-medical applications

Near-infrared (NIR) light-excited fluorescence is gaining increasing attention as an analytical tool (in molecular probes) as well as for performing in vitro /in vivo imaging of individual cells and organs. The NIR region (700-1100 nm) is ideal with regard to these applications due to the inherently lower background interference and deep penetration of NIR light into tissues. Therefore, the NIR region is also attractive for several medical applications, including photodynamic therapy (PDT), where the deep penetration of light into tissues is of crucial importance.

PDT is a minimally-invasive cancer treatment modality requiring activation of a photosensitizer for light-mediated tumor cytotoxicity. PDT utilizes a photosensitizer, working as a light-sensitive drug, to treat the target tissue locally upon the irradiation of light with appropriate wavelengths. It is generally accepted that the mechanism of PDT is based on the interaction between the excited photosensitizer and surrounding molecules, generating reactive oxygen species (ROS). In PDT, photo-sensitized ROS, e.g. singlet oxygen (1Δg), cause oxidative damage to biological targets within diseased tissues, thus leading to cellular damage and ultimately cell death.

Energy level diagram of Yb3+/Er3+ ion pair in an up-converting phosphor (left panel). Green light emission from the custom-synthesized up-converting NaYF4:Yb,Er phosphor under excitation with 980 nm light (right panel).

Since the local emission of the visible light is a prerequisite for both bio-imaging and PDT, there is an increasing interest in developing bio-compatible up-converting systems.  In particular, inorganic, sub-micron to nano-sized up-converting phosphors (nano-UPs) draw more and more attention due to their potential applications in bio-imaging and bio-medicine. A large anti-Stokes shift (up to 500 nm) observed in these materials separates discrete emission peaks from the infrared excitation source. Along with the unmatched contrast in biological specimens (due to the absence of auto-fluorescence upon infrared excitation), up-converting phosphor technology has unique properties for highly-sensitive particle-based assays and for performing deep-tissue photo-oxidations (such as in PDT).  Thus, these materials, very often based on NaYF4:Yb3+/Er3+ phosphors, are capable of absorbing photons of low energy (e.g. in the NIR range at λex = 980 nm) and emitting photons with high energy (in the visible range at λem ~ 550 nm). This can be seen in FIGURE 4.

We are interested in physical and photo-physical aspects of inorganic up-converting materials. Our goal is to develop efficient up-converting systems and thoroughly characterize them using several spectroscopic techniques, such as: transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS) and electron spin resonance (ESR).

This research should make it possible to prepare efficient up-converting phosphors with high photo-dynamic efficiencies and bring them closer to bio-medical applications, including PDT and novel systems, like bio-sensors and bio-inspired materials [1, 2].
[1] M. Crittin, I. Ahmadov, M. Ramazanov, M. Schaer, L. Forró, and A. Sienkiewicz, “Bioimaging using up-converting nanophosphors”, contributed talk at the Symposium: Bio-nanomaterials for imaging, sensing and actuating, E-MRS Spring Meeting Conference, Nice, May 9-13, 2011
[2] M. Crittin, K. Pierzchała, L. Forró, and A. Sienkiewicz, “Nano-structured up-converting photo-sensitizers of singlet oxygen (1Dg) – Electron Spin Resonance study”. Conference: Nano-Bio-Sensing EPFL, 29 June – 3 July 2009, EPFL, Lausanne, Switzerland.