New Cutting Edge Paper from Dr. McFarland and Colleagues One of the problems with light activated photosensitizers is that light only provides limited penetration of tissue. The green light used in the current NMIBC trial, for example, can only penetrate to a depth of 1.5 mm but that is all that is needed to treat NMIBC. For other indications new techniques will need to be developed.
X-rays can penetrate tissue much deeper but can activate currently used photosenstizers to only a limited extent. To get around this limitation researchers have proposed the use of nanoscintillators to mediate the X-rays. The McFarland Group, in collaboration with Dr. Lilge and researchers from the University of Alberta have developed a new nanoscintillator along with a new Ruthenium based photosensitizer to facilitate X-PDT.
The following paper by Chinese and American researchers explains why nanoscintillators are required.
Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications
"The energy of X-rays used in clinical Radiation Therapy is in the range of hundreds of keV to MeV. As a result, most traditional photosensitizers used for cancer PDT cannot be effectively activated by X-rays. In this regard, a physical transducer is required to absorb the X-ray irradiation energy and transfer it to photosensitizers to produce the cytotoxic singlet oxygen (1O2) necessary for tumor destruction. In the classical X-PDT model, this energy transfer is achieved by converting the absorbed x-ray energy into optical photons of the appropriate wavelength that can be absorbed effectively by photosensitizers. These transducers are generally called scintillators and exhibit X-ray excited optical luminescence (XEOL). "
Here is a link to the abstract of Dr. McFarland's new paper:
High Quantum Efficiency Ruthenium Coordination Complex Photosensitizer for Improved Radiation-activated Photodynamic Therapy (radioPDT)
"Traditional external light-based Photodynamic Therapy (PDT)'s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiationactivated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A key consideration in radioPDT is the energy transfer efficiency from X-rays to the photosensitizer for ultimately generating the phototoxic reactive oxygen species (ROS). In this study, we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSCs) along with a new, highly efficient ruthenium-based photosensitizer (Ru/radioPDT). Characterization of this NP via transmission electron microscopy, dynamic light scattering, UV-Vis spectroscopy, and inductively coupled plasma mass-spectroscopy showed an NP size of 120 nm, polydispersity index (PDI) of less than 0.25, high NSCs loading efficiency over 90% and in vitro accumulation within the cytosolic structure of endoplasmic reticulum and lysosome. The therapeutic efficacy of Ru/radioPDT was determined using PC3 cell viability and clonogenic assays. Ru/radioPDT exhibited minimal cell toxicity until activated by radiation to induce significant cancer cell kill over radiation alone. Compared to protoporphyrin IX-mediated radioPDT (PPIX/radioPDT), Ru/radioPDT showed higher capacity for singlet oxygen generation, maintaining a comparable cytotoxic effect on PC3 cells."