Summary

Since the discovery of cisplatin about 40 years ago, the design of innovative metal-based anticancer drugs is a growing area of research. Metal elements offer specific characteristics due to their intrinsic properties and could be used in relation to their final state: a metal complex, a radionuclide, a metal-based nanoparticle product. Transition metal coordination complexes interact with cell molecular targets, affecting biochemical functions resulting in cancer cell destruction. Radionuclides are another way to use metals as anticancer therapy. The metal nucleus of the unstable radionuclide becomes stable by emitting energy. The biological effect in different tissues is obtained by the absorption of this energy from the radiation emitted by the radionuclide, the principal target generally agreed for ionizing radiations being DNA. A new area of clinical research is now emerging using the same experimental metal elements, but in a radically different manner: metals and metal oxides used as crystalline nanosized radiation enhancers particles. The use of metals as a high electron density material tailored at the nanoscale when exposed to radiotherapy is a unique approach that can allow entry to the cell and make feasible the absorption/deposition of a high-energy dose within the tumor cell (on/off activity). Therefore, high electron density metal or metal oxide nanoparticles may bring well known physical mode of action, that of radiotherapy, within malignant cells and achieve the paradigm of local cancer treatment.

Summary

Congress: CLINAM, 23rd May 2011

Contents: The development of new activatable drug nanocarriers, with multiple functionalities, presents a promising approach for cancer treatment.

Improved drug delivery and controlled drug release at the tumor site may have considerable benefit by increasing treatment efficacy while reducing side effects and toxicity. Further, the possibility to monitor both nanocarrier accumulation and drug release via current clinical imaging techniques may be particularly relevant for an optimal treatment.

Within the European project “Sonodrugs”, we investigated the opportunity of triggering the drug release from new nanocarriers (temperature and pressure-sensitive) thanks to High Intensity Focused Ultrasounds (HIFU) and monitoring the release profile of the drug at the tumor site thanks to Magnetic Resonance Imaging (MRI) imaging.

A new versatile thermosensitive liposome has been designed and developed to efficiently encapsulate a drug (doxorubicin) and a contrast agent (superparamagnetic iron oxide nanoparticles).

Summary

Full Title: NBTXR3 hafnium oxide nanoparticle activated by ionizing radiation demonstrates marked radioenhancement and antitumor effect via high energy deposit in human soft tissue sarcoma

Content: Local and systemic control of Soft Tissue Sarcoma (STS) remains a clinical challenge. Radiation therapy is part of the standard of care of STS. The narrowness of its therapeutic window represents the main concern for different clinical settings. Thus, local delivery of radiation doses is critical to ensure optimal benefit-risk ratio. NBTXR3, biocompatible hafnium oxide nanoparticles were designed as therapeutics to be activated by ionizing radiation to achieve tumor control by enhancement of local energy deposition.