ABSTRACT

This CAREER project is a part of a global effort to conquer cancer, the second leading cause of death. Despite the enormous investments in research and development, there have been scant clinical successes as a viable cancer therapy. Recent advancements in cancer therapy have resulted in the emergence of implanted medical devices (IMDs) into feasible medicines, owing to their capacity to localize treatments, albeit limited in numbers. However, currently available IMDs-mediated cancer treatments are often confined to a single, non-replenishable administration per therapy. These limitations, along with a number of risks such as painful surgery, infection risk in the catheter, and device failure, have generally hampered the usage of IMDs in cancer treatment. More importantly, cancer cannot be effectively managed with a single therapeutic approach due to its complex, diverse, and heterogeneous nature. As such, this CAREER project investigates a versatile engineering solution in the form of an acoustically driven implantable microsystem that provides a tailored combination of multimodal cancer therapeutics: oxygen, chemotherapy drugs, and light. Combined, this project aims to establish the field of ?Acousto-Bioelectronics? that spurs new theory and understanding for the next generation of IMDs. Furthermore, the project integrates the research with educational venues by mentoring graduate and undergraduate students, with a particular emphasis on the underrepresented minorities and female students, developing interdisciplinary curricula, and creating pedagogical resources ranging from fundamental theory to hands-on activities.

While IMDs are transforming modern healthcare, they are unable to cure cancer at the moment due to their short lifetime. This is compounded by the fact that many cancers can relapse or spread metastatically. The overarching goal of this CAREER project is to leverage cross-cutting innovations from the domain of engineering and healthcare fields to create an ultrasonically-powered implantable microsystem that enables a tailored combination of multimodal cancer therapies. This study (1) elucidates the untapped potential of Platonic solid structures for a highly efficient omnidirectional ultrasonic powering scheme for IMDs, utilizing a unique 3D-printable barium titanate ultrasonic receiver. (2) Providing adequate power via ultrasound, the microsystem enables the in-situ generation of oxygen, cisplatin, and light through controlled electrochemical and photochemical processes. It is hence called Oxygen Enhanced Chemo-Photodynamic Therapy. (3) The microsystem can potentially realize clinically-proven superadditive anticancer effect ? stronger than any single therapy or theoretical combination. The microsystem-mediated multimodal cancer therapy would be validated through a comprehensive evaluation by employing clinically relevant models (in vitro and in vivo cancer models). The outcome of this project justifies the development of the IMD-mediated multimodal cancer therapy that will potentially help patients suffering from aggressive and fatal cancer types with limited treatment alternatives.

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.

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