Johns Hopkins Center of Cancer Nanotechnology Excellence
Johns Hopkins University
Peter Searson, Ph.D.
Martin Pomper, M.D., Ph.D.
Project 1: Screening DNA Methylation in Bodily Fluids for Early Cancer Diagnostics and Therapeutic Monitoring
Project Investigators: Jeff Wang, Ph.D., Stephen Baylin, M.D., and James Herman, M.D.
Gene inactivation by promoter hypermethylation can occur at early stages of cancer progression, potentially before mutations can be detected. Using DNA methylation as a cancer biomarker shows great promise for early diagnosis, assessment in high-risk individuals, and post-therapy monitoring. This Project will develop a new integrated, chip-based platform for methylation detection that integrates improved methods for DNA isolation, bisulfite treatment, and detection of methylation using a quantum dot biosensor. The platform will be tested in preclinical studies by testing samples from patients with early stage cancers.
Project 2: Systemic Nanocurcumin for Pancreatic Cancer Therapy
Project Investigators: Anirban Maitra, M.D., and Martin Pomper, M.D., Ph.D.
Although the anti-cancer and chemopreventive properties of curcumin have been established, the clinical translation has been significantly hampered due to its poor oral bioavailability. This Project seeks to overcome this barrier by engineering polymeric nanoparticles that are capable of solubilizing poorly water-soluble drugs such as curcumin, providing a new approach for pancreatic cancer therapy.
Project 3: Noninvasive Quantification of Vaccine-Mediated Antigen Delivery to Lymph Node by Magnetic Resonance Imaging
Project Investigators: Hy Levitsky, M.D., and Jeff Bulte, Ph.D.
A major parameter limiting immune responses to vaccination is the number of appropriately activated antigen presenting cells (APCs) that capture antigen from the vaccine site and migrate to draining lymph nodes (LNs). A quantitative tool to noninvasively monitor these early events post-vaccination would greatly facilitate the clinical development of therapeutic cancer vaccines. Researchers have developed an in vivo tool where tumor cell–based vaccines are labeled with superparamagnetic iron oxide (SPIO) nanoparticles as a magnetic resonance contrast agent. MRI is used to monitor the trafficking of magnetically labeled antigen presenting cells that are responsible for inducing tumor-specific immune responses. Using this approach, this Project will evaluate candidate vaccine adjuvants for their ability to augment this critical step in generating systemic immunity. This Project will also extend magnetovaccination technology in preclinical lung cancer models to therapeutic cancer vaccine platforms and APC targeted monoclonal antibody vaccine approaches.
Project 4: Mucus Penetrating Nanoparticles for Small-Cell Lung Cancer
Project Investigators: Justin Hanes, Ph.D., Charles Rudin, M.D., Ph.D., and Craig Peacock, Ph.D.
Drugs delivered locally to the lung airways (via inhalation) are typically cleared rapidly by systemic absorption combined with the mucus clearance mechanism. Researchers have developed mucus-penetrating nanoparticles (MPP) coated with non-mucoadhesive polymers that are capable of providing delivery of controlled concentrations of drug locally to the lung airways over more sustained periods than previously possible with conventional nanotechnologies. By penetrating the surface mucus layer, it is possible to avoid rapid elimination from the lung airways, provide prolonged delivery of chemotherapeutics locally, minimize systemic toxicity, and significantly improve drug efficacy. This Project will evaluate the pharmacokinetics and efficacy of biodegradable MPP loaded with frontline chemotherapeutic agents for small-cell lung cancer therapy.