Bioconjugates of photon-upconversion nanoparticles for cancer biomarker detection and imaging
Photon-upconversion nanoparticles that convert two or more low-energy photons to one photon of UV, visible or NIR light enable the detection and imaging of cancer markers without optical background interference.
Cancer is, after cardiovascular diseases, the second leading cause of death worldwide with nearly 10 million deaths in 2020 (WHO). While the number of cancer cases is still on the rise as an adverse side effect of longer life expectancies, advances in the early detection and optimal treatment of cancer have led to a significant reduction in disease relapse and death over the last few decades. The sensitive detection of cancer biomarkers in histological samples and blood by immunochemical techniques is a cornerstone of cancer diagnosis. However, current immunochemical techniques fall short of expectations in terms of sensitivity and specificity, hindering early disease diagnosis.
Photon-upconversion nanoparticles (UCNPs) emit short-wavelength light under near-infrared excitation, allowing the detection and imaging of cancer markers without optical background interference. Already 20 years ago, the potential of UCNPs for histology had been recognized, but only the synthesis of well-defined and transparent nanocrystals made these nanoparticles widely applicable for biomedical applications. The development of the upconversion technique requires close cooperation between physicists, chemists, and biologists. From 2014 to 2018, we thus established the multidisciplinary COST Action “The European Upconversion network – From the design of photon-upconverting nanoparticles to biomedical applications” and a biannual conference series to address such diverse aspects as upconversion enhancement, surface functionalization, instrument development, bioanalytical applications, and toxicity.
Research on upconversion is rapidly progressing and many different materials and bioconjugation strategies are developed every day. Our protocols include the synthesis of inorganic nanocrystals, new spectroscopic instruments, surface and bioconjugation chemistry as well as biomedical applications. This multidisciplinary approach has been essential for developing a powerful platform for cancer diagnosis.
We developed a highly sensitive upconversion-linked immunoassay (ULISA) for the detection of prostate-specific antigen (PSA), which is an important biomarker for prostate cancer. When switching from a conventional (analog) readout mode to counting of individual immune complexes (digital readout), the sensitivity was further enhanced by a factor of 20 such that subfemtomolar concentrations of PSA were detectable.
Additionally, we detected the breast cancer marker human epidermal growth factor receptor 2 (HER2) by immunocytochemistry with an unprecedented signal-to-background ratio of more than 300, which is 50-fold better compared to conventional fluorescence detection. This approach has found its way into industry.
Lumito works together with experts from academia to keep up with the fast-evolving field of photon upconversion. The unique photophysical properties of UCNPs are especially suitable for digital tissue diagnostics. The upconversion process completely prevents autofluorescence which can be very pronounced in fixated tissue samples. The low background paired with an efficient detection method causes a high signal-to-background ratio that is beneficial for digital image evaluation. Lumito develops a reagent-kit tailored to deliver high contrast images of UCNP-labelled tissue samples obtained from a fully automatic whole-slide upconversion laser scanner. With this system Lumito wants to ease the work of pathologists and pave the way for faster and more accurate digital tissue diagnostics.