Clover Project

Photoactivatable nanocomposite systems for MRI-guided minimally invasive glioblastoma therapy

Skoltech: PI - Prof. Dmitry Gorin
Project team:Dr. Sergey German, Julijna Cvjetinovic, Ekaterina Moiseeva, Maksim Mokrousov, Igor Sergreev

ITMO: PI - Prof. Anna Orlova
Project team: Dr. Viktor Zakharov, Ilia Vovk, Tonya Dadadzhanova, Maxim Rider, Ekaterina Smirnova, Konstantin Baranov, Tatiana Oskolkova

MIPT: PI - Dr. Sergey Novikov
Project team: Dr. Ilya Zavidovsky, Mikhail Tatmyshevskiy

The project is aimed at creating a minimally invasive technology for the treatment of malignant neoplasms based on the latest achievements in photonics, materials science of nanostructured materials, and biophysics. The problem of precision focused destructive effects on solid tumors is particularly acute in the case of minimally invasive therapy of brain malignancies. One of the approaches to solving this problem is associated with the creation of local distributed sources of photoexcitation as a result of cavitation effects initiated by ultrasonic radiation. The presence of such sources, whose energy is sufficient to activate photosensitizers of reactive oxygen species (ROS) inside the tumor, will allow using all the advantages of traditional photodynamic therapy (PDT) (minimally invasive, high specificity for tumor tissue and low toxicity for healthy tissues, high efficiency), overcoming one of its key drawbacks - a small penetration depth electromagnetic radiation of the optical range into biological tissues. The availability of high-tech clinical equipment that allows for hyperthermia of pathological tissue with focused ultrasound under MRI/ultrasound control makes the idea of developing an analogue of PDT, in which the occurrence of local sources of excitation is initiated by ultrasound exposure, especially attractive and relevant. The implementation of this idea can be successfully carried out using the latest developments in the field of nanostructure materials science, which allow creating multifunctional composites combining ROS photosensitizers, iron oxide nanoparticles for MRI imaging and vectors for targeted delivery. Within the framework of the given project, it is proposed: 1) to develop MRI contrasting nanostructured composites demonstrating the effective generation of reactive oxygen species under the influence of electromagnetic radiation and focused ultrasound; 2) to conduct a theoretical and experimental study of the occurrence of local sources of photoexcitation under the action of ultrasound of a given frequency and intensity, as well as the effectiveness of their use for the activation of molecular and nanostructured photosensitizers ROS as part of nanostructured composites; 3) to carry out a study of the effectiveness of the functioning of composites in vitro, ex vivo and in vivo.