Co-development and clinical translation of nanomedicines
My group co-develops and translates molecularly-targeted, ultrasmall fluorescent silica nanoparticles (C’ dots) to the clinic for image-guided surgical and therapeutic applications in cancer and related diseases. Radiolabeled fluorescent C’ dots are used for multimodal imaging and to assess pharmacokinetic and safety profiles, while attachment of therapeutic labels are used for radiotherapeutic applications (FDA-cleared INDs, 2011; 2013; 2019; 2024).
Modulation of the tumor microenvironment
The multitherapeutic properties of C’ dots are utilized by my group to modulate/activate and/or downregulate different tumor and immune cell populations within solid tumor microenvironments, as well as induce cell death mechanisms – both serving to maximize efficacy and enhance the performance of immunotherapies, including checkpoint inhibitors and CAR T cells. Data is used to inform novel combinatorial strategies to reduce immune suppression and limit resistance associated with conventional treatments (e.g., immune-/chemo-/hormone therapy), as well as uncover new therapeutic targets and biomarkers.
Synthetic Biology
My group is engaged in protein engineering and the development of novel targeted biologics, cellular engineering systems, and microbial (probiotic-driven) constructs for use with nanomedicines and as combinatorial partners for the diagnosis and treatment of disease.
Fluorescence-guided intraoperative multiplexing and theranostics
A collaborative research agreement with Olympus has expanded the use of intraoperative technologies for multiplexed detection and theranostics. We utilize a multichannel fluorescence camera system and either open or laparoscopic imaging tools for imaging and treating disease (and/or normal tissue targets) in both preclinical models and patients. Perfusion imaging can also be used as part of novel paradigms for treatment planning. Early efforts are focused on machine learning algorithms that enable best imaging and response parameters to be established for specific applications.
Enhancing Tumor-targeted Drug Delivery
By conjugating small molecule drugs and/or therapeutic radiolabels to C’ dots via different types of linkers, we have significantly improved the targeted delivery, penetration, and accumulation of these therapies to enhance efficacy and therapeutic indices in a variety of solid tumors. We carefully control surface chemical designs to achieve favorable whole-body distributions, monitored using quantitative PET imaging. This supports product translation and batch-to-batch reproducibility.
Super-resolution Microscopy
My group utilizes super-resolution microscopy tools for visualizing and quantifying alterations in highly-expressed tumor- and immune-specific molecular markers in the primary and metastatic tumor microenvironments, as well as cell-cell interactions. Findings will be correlated with other multiplex imaging technologies, such as the Hyperion, which the Precision Medicine Institute employs for mass spectrometry-based scanning of clinical and research specimens.