A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo

Photodynamic therapy for cancer: principles, clinical applications and nano technological approaches

Photodynamic therapy (PDT) is a clinically approved, minimally invasive procedure that can exert a cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizer (PS) followed by irradiation with light at wavelengths within of the PS absorption band. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies reveal that PDT can be curative, particularly in early stage tumors, can prolong survival in patients with inoperable cancers, and can significantly improve quality of life. Unfortunately, most PS lack specificity for tumor cells and this can result in undesirable side effects in healthy tissues. Furthermore, due to their mostly planar structure, PS form aggregates with low photoactivity in an aqueous environment. Nanotechnology offers a great opportunity in PDT based on the concept that a nanocarrier can drive therapeutic concentrations of PS to the tumor cells without generating any harmful effect in vivo. Currently, several nanoscale carriers made of different materials such as lipids, polymers, metals, and inorganic materials have been proposed in nano-PDT. Each type of system highlights pros and cons and should be selected on the basis of delivery requirements. In the following, we describe the principle of PDT and its application in the treatment of cancer. Then, we illustrate the main systems proposed for nano-PDT that demonstrated potential in preclinical models together with emerging concepts for their advanced design