Nanoparticles for the Detection of Early Lung Cancer

K. Anderson, T. Dziubla, Z. Hilt, M. Knecht, H. Mansour, E. Bensadoun

Currently, no clinically useful non-invasive test exists to evaluate small pulmonary nodules found in as many as 50% of patients during CT screening. Although >95% of nodules are benign, they all have the potential to be malignant and require a thorough evaluation. Nanotechnology and nanoimaging techniques may lead to non-invasive tests to detect malignancy within pulmonary nodules. This project combines the expertise of Bensadoun in lung cancer diagnostics and treatment with those of investigators from the Pharmaceutical Sciences (Mansour), Chemistry (Knecht), and Engineering (Anderson, Dziubla, and Hilt) who focus on selective pulmonary drug delivery and the development and characterization of nanoparticles for diagnostic and therapeutic applications.

Multiple mechanisms using nanoparticles will be evaluated in an effort to detect the presence of malignancy within small nodules. Specifically, trainees will investigate methods of selective delivery of nanoparticles to pulmonary nodules. It is hypothesized that if nanoparticles could be delivered selectively to malignant tissue, MRI could then be used to detect malignancy within small pulmonary nodules. Selective delivery may be achievable by coupling nanoparticles to deoxyglucose which accumulates in tumors at higher concentrations than in normal tissues. Trainees working with Anderson, Hilt and Knecht will develop and characterize iron oxide nanoparticles that display deoxyglucose on the particle surface for in vivo tumor recognition.

Mansour and Dziubla will mentor trainees developing other selective delivery modes, for example, ligands specific for receptors that are upregulated and overexpressed in lung cancer cellular membranes or the associated vasculature. In addition, trainees working with Mansour will develop inhalation aerosols of precise aerodynamic size containing targeting ligands shown to be effective in cell culture on their surface to enhance tumor selectivity in specific lung airway regions. Once these particles are developed and characterized, Bensadoun will mentor trainees to enhance the resolution in nanoimaging of lung cancer cells by incorporating clinically approved technetium (99mTc) labelling into the nanoparticles. Alternatively, small nodules which are expected to possess disturbed flow patterns, can be imaged by accumulation of iron oxide loaded worm-like polymeric micelles (Dziubla) or biomimetic nanoliposomes (Mansour) into these disturbed flow domains. Bensadoun will also oversee in vivo and ultimately clinical studies of the selective delivery and diagnostic capabilities of these systems.