Non-Technical Abstract Nano-sized materials that disassemble on demand can release therapeutic agents to sites where they are most needed. Light is an especially promising tool for triggering this on-demand carrier disintegration: it can pass through many barriers, be directed to precise locations, and be switched on and off easily. Most current biologically relevant technologies use high energy ultraviolet (UV) and visible light that do not penetrate tissue significantly. The research groups of Professor Samuel Thomas at Tufts University and Professor Vincent Rotello at the University of Massachusetts Amherst are working to overcome this limitation in therapeutic delivery by designing, developing, and understanding the ability of nano-sized materials to disintegrate upon exposure to low energy near-infrared (NIR) light. NIR light penetrates tissue to far greater depths than UV or visible light, providing access to new biological applications. They will gain understanding into how chemical design influences nanomaterial response to NIR light, and these materials will be further elaborated to target and deliver therapeutics to both cancer cells and bacterial biofilms. This research has the potential to benefit society through creation of new nanomaterials that harness NIR light to selectively deliver drugs and mitigate harmful side effects. Beyond the hands-on interdisciplinary training that this research provides to more graduate students, this project also provides targeted support for disadvantaged high school students to undertake research through the Tufts Summer Research Experience, thereby broadening participation in the STEM disciplines.
With support from the Biomaterials Program of the NSF Division of Materials Research, the goal of this research is to establish the ability of micelles in vitro to be degraded by singlet oxygen prepared in situ using NIR light. The overall project goal is to understand how chemical structures and polymer assemblies influence key individual chemical and physical material characteristics relevant to drug delivery. The first phase of this project will be to prepare and characterize polymers and micelles with a range of singlet oxygen-cleavable linkers, reactivities, and polymer topologies. The second phase of this project will be to understand how chemical structure and nanomaterial composition determines loading of cargo, stability in serum, photodegradation, and triggered release. The third stage of this project will evaluate the in vitro cytotoxicity and anti-bacterial activity of cargo-loaded NIR-degradable micelles. Further extension of this understanding of fundamental structure-property relationships will include micelles with targeting groups on their surfaces such as the RGD motif for cancer cells and quaternary ammonium cations for bacterial biofilms. Overall, this work has the potential to improve the efficacy of light-responsive drug-delivery systems, and in a broader context, advance the field of stimuli-responsive biomaterials by correlating chemical structures and their assemblies with loading, release, and in vitro activity.
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.
