FERRITIN-BASED TUMOR TARGETING AGENT, AND IMAGING AND TREATMENT METHODS

摘要

An MRI contrast material includes tumor-targeting metal-loaded ferritin nanoparticles constructed with genetically modified ferritin coupled to a target-specific agent. Ferritin derived from Archaeoglobus fulgidus (AfFtn-AA) forms hollow nanocages surrounding paramagnetic or superparamagnetic metal core, storing a significantly greater quantity of iron (approximately 7,000 Fe ions per ferritin cage) or other paramagnetic or superparamagnetic metal than natural ferritins, and is conjugated via a short linker with a monoclonal antibody against a cell surface antigen overexpressed by a cancer, to selectively and efficiently attach to tumor cells to enhance MRI contrast. Significant T2 contrast with diminished T1 effect was observed owing to the heterogeneous nanoconjugate distribution when bound to cells. In a treatment method, after imaging, an external stimulus heats the cell-bound agent to release the metal and selectively destroy the targeted cells. The enhanced imaging and release of toxic metal ions provides simultaneous early detection and treatment.