Project Investigator: Ulrich Wiesner, PhD
The primary objective of Project 1, a basic research effort led by Ulrich Wiesner, is the synthesis and exploration of novel classes of < 10 nm C dots synthesized in water for use as cancer-targeted diagnostic and therapeutic probes. Major goals include using high-resolution analytical tools to characterize variations in particle size, composition, geometry, surface chemistry, and material heterogeneity, and correlating these variations with pharmacokinetics, renal clearance, and tumor-to-background ratios in melanoma models. Expected outcomes are correlations of particle structures with biological properties enabling economic particle synthesis in water and clinical translation.
Project Investigators: Michelle Bradbury, MD, PhD, and Snehal Patel, MD
The primary objective of Project 2, a translational research effort led by Michelle Bradbury and Snehal Patel, is the optimization of new-generation C dots for earlier and more reliable detection of multiple targets on melanoma-bearing lymph nodes and / or adjacent nerves, using an FDA-approved handheld intraoperative fluorescence camera. Major goals include development and screening of NIR dye-containing melanoma-targeting particles; selection of lead candidates to assess tumor-specific accumulation and pharmacokinetic profiles in conventional / GEMM animal models; and development of spectrally distinct NIR dye-containing products for simultaneous differentiation of distinct pathological markers on diseased nodal tissue and normal tissue types. Expected outcomes include novel image-guided multiplexing tools to visualize both disease and normal critical structures for better surgical management and reduced surgical risks.
Targeted Ultrasmall Silica Nanoparticles for Alpha- and Beta-Emitting Radiotherapy and Delivery of Small Molecule Inhibitors
Project Investigators: Thomas Quinn, PhD; Michael McDevitt, PhD; Cameron Brennan, MD; and Charles Rudin, MD, PhD
The primary objectives of translational research Project 3 are to target radiolabeled C dots to melanoma to deliver highly localized radiation doses and to deliver and release SMIs from nanoparticle-drug conjugates (NDCs) to malignant brain tumors. Melanoma studies will be led by Thomas Quinn and Michael McDevitt. 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 effective 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 and Charles Rudin, 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.