Targeted Ultrasmall Silica Nanoparticles for Alpha- and Beta-Emitting Radiotherapy

The primary objectives of translational research Project 3 are to (1) target radiolabeled C dots to melanoma to deliver highly localized radiation doses and (2) deliver and release SMIs from nanoparticle-drug conjugates (NDCs) to malignant brain tumors.

Melanoma studies will be led by Thomas Quinn, Professor of Biochemistry, University of Missouri, with co-lead Michael McDevitt, Radiologist, MSKCC. Major goals for melanoma models include the generation of optimized targeted C dots exhibiting favorable biological properties in melanoma models, as well as the development of safe and efficacious alpha- and beta-emitting C dots for clinical translation. Expected outcomes include the advancement of targeted C dot radiotherapeutics as part of combinatorial treatment paradigms with immunotherapies to improve melanoma management. Major goals of the malignant brain tumor studies, led by Cameron Brennan, M.D., Associate Member, Human Oncology and Pathogenesis Program, Sloan Kettering Institute, and Associate Professor of Neurosurgery, Weill Cornell Medical Center with co-lead Charles Rudin, M.D., Ph.D., Chief, Thoracic Oncology, MSKCC, will include the creation of optimized NDCs that exhibit favorable biological properties and overcome dose-limiting toxicity for use in combinatorial brain tumor treatment strategies. Expected outcomes include the development of potent NDCs with improved PK profiles, tumor accumulation, and enhanced therapeutic index.