Engineering\nMesoporous Silica Nanoparticles for Targeted Alpha Therapy against\nBreast Cancer

Abstract

Targeted alpha therapy,\nwhere highly cytotoxic doses are delivered to tumor cells while sparing\nsurrounding healthy tissue, has emerged as a promising treatment against\ncancer. Radionuclide conjugation with targeting vectors and dose confinement,\nhowever, are still limiting factors for the widespread application\nof this therapy. In the current study, we developed multifunctional\nsilica nanoconstructs for targeted alpha therapy that show targeting\ncapabilities against breast cancer cells, cytotoxic responses at therapeutic\ndosages, and enhanced clearance. The silica nanoparticles were conjugated\nto transferrin, which promoted particle accumulation in cancerous\ncells, and 3,4,3-LI­(1,2-HOPO), a chelator with high selectivity and\nbinding affinity for f-block elements. High cytotoxic effects were\nobserved when the nanoparticles were loaded with ²²⁵Ac,\na clinically relevant radioisotope. Lastly, <i>in vivo</i> studies in mice showed that the administration of radionuclides\nwith nanoparticles enhanced their excretion and minimized their deposition\nin bones. These results highlight the potential of multifunctional\nsilica nanoparticles as delivery systems for targeted alpha therapy\nand offer insight into design rules for the development of new nanotherapeutic\nagents.