Collaborative Research: Design and mechanistic studies on microenvironment-sensitive polymeric nanoparticles for simultaneous contents release and ultrasound imaging

Non-technical Description: Many diseases, such as cancer, are dreadful because often, they are diagnosed late when therapy proves ineffective. Moreover, when therapy is available, it involves debilitating side effects, including other life-threatening conditions. The primary healthcare objectives, therefore, are early, noninvasive accurate diagnosis and effective therapeutic intervention without harmful side effects. Here a cross-disciplinary scientific team led by a pharmaceutical chemist and an engineer from two universities will develop and study the fundamental science behind a single clinical implement with the dual aim of improved diagnostic ultrasound imaging and targeted therapy which becomes active only in the target region. The team aims at synthesizing nanometer-size polymeric particles. They are similar in structure to body cells and can carry therapeutics to target areas evading the body’s defense system. The particles are chemically engineered to implode in a specific chemical environment found only in diseased conditions and deliver their cargo. The proposed research will systematically investigate the chemistry of these nanoparticles through experiments and theory to optimize their desired effects and the mechanism behind their ultrasound reflectivity. The principal investigators have proposed an array of educational activities involving high school interns, undergraduates, and Ph.D. students in multi-disciplinary projects with real-life clinical applications preparing them to enter the twenty-first-century workforce. Technical Description: The objective of this proposal is to conduct foundational studies on polymer nanoparticles (polymersomes) that are programmed to release their encapsulated contents under specific biochemical environments common in diseases and simultaneously are responsive to ultrasound to allow imaging and ultrasound-assisted release. It uses reduced oxygen partial pressure as a model trigger for release. The proposed studies will develop the design principles of multimodal polymer nanoparticles for future applications in drug delivery to tumors and simultaneous ultrasound imaging. The team will optimize polymer design so that the resultant polymersomes become responsive to the reduced oxygen levels and release the encapsulated contents. The nanoparticles will be made to entrap air allowing simultaneous ultrasound imaging before their destruction. These echogenic content-bearing polymersomes will be tested in three-dimensional (3D) cultures of cancer cells containing hypoxic niches. The award will support activities that broaden participation in research and education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.