Targeted Drug Delivery
Targeted delivery of therapeutic agents represents an exciting research direction since it can mitigate harmful off-target effects that are characteristic of many drug entities. In addition, by outfitting a drug with an imaging beacon, we can noninvasively track delivery in vivo using state-of-the-art imaging techniques.
An example of this approach is highlighted by the development of PARx, a glutathione-responsive prodrug, designed to treat lung cancer (Nat Chem 2021). Glutathione is typically not considered to be a good disease biomarker because it is abundant throughout the body. However, we were able to successfully fine-tune the chemical reactivity of a new trigger to distinguish healthy tissue from lung tumors with exquisite selectivity. Researchers working in this area will learn how to design disease-responsive triggers which will be employed to mask the cytotoxic properties of a drug until it is released by an aberrant molecular feature targeted in the disease tissue.
A complimentary approach is to initiate the delivery of drugs using light. Light in the NIR (650-900 nm) and SWIR (900-1300 nm) windows are generally safe and can be focused onto a specific region of the body to enable on-demand and site-selective drug release. For instance, photoNOD is a chemical designed to halt the growth of breast tumors via the release of nitric oxide (JACS 2018) and NIR-nanogel is nanoparticle system that can be induced to fragment, allowing for delivery of the encapsulated drug cargo (JACS 2022). Researchers working on these projects will learn how to synthesize complex molecules, as well as to fabricate nanoparticles that are sensitive to light.