Investigator: Stephen Kennedy, University of Rhode Island
Mentor: Lu Wei, University of Rhode Island
Scientific Theme: Cancer
Abstract: This proposed work broadly aims to optimize the temporal delivery profiles of chemotherapeutics and develop biomaterial systems that are capable of producing these delivery profiles after implantation. The long-term objective of this line of research is to enhance tumor regression and patient survival by locally delivering complex chemotherapeutic temporal profiles from implanted biomaterial systems. Aim 1 of this work will be to assess the impact of different chemotherapeutic temporal profiles on mouse melanoma cell survival in vitro. We will quantify B16-F10 mouse melanoma cell viability when subjected to various chemotherapeutics with various concentration profiles over time. We will investigate this for 4 common chemotherapeutics that have different cytotoxic mechanisms on cancer cells. Aim 2 will be to develop biomaterial systems that are capable of flexibly coordinating complex chemotherapeutic delivery profiles in response to externally applied cues. We will utilize methodologies developed in our lab to electrically, magnetically, and/or ultrasonically trigger the release of chemotherapeutics from implantable hydrogel systems. Complex delivery profiles will be achieved by designing these hydrogels to (i) release very little drug when unstimulated by exploiting electrostatic drug-scaffold interactions, (ii) only appreciably deliver drug when stimulated, and (iii) release drug at a rate that is prescribed by characteristics of the remotely applied signal (e.g. amplitude, frequency, and spatial distribution of the field). These biomaterial systems will not only be able to produce the optimized drug delivery profiles established in Aim 1, but also provide clinicians with the needed flexibility to alter delivery doses in real-time in response to changes in patient prognoses.
Human Health Relevance: This proposed research will expand our knowledge of how the temporal delivery profile of various chemotherapeutics impacts cancer cell viability. It will also innovatively utilize remotely activated biomaterials to develop implantable systems that are capable of delivering optimized therapeutic profiles directly to tumor sites. These are critical preliminary steps towards developing improved strategies in cancer treatment.