The Art of Falling Apart: On-demand Release from Polymeric Carriers

C. de Gracia Lux, M.L. Viger, N. Fomina, J.E. Olejniczak, A. Almutairi
University of Californi, San Diego, US

Keywords: on-demand release, triggered release, light-sensitive, bioresponsive


The conventional approach to delivering drugs to diseased tissues is to encapsulate drugs into nanocarriers decorated with peptides or aptamers that specifically bind disease-associated receptors. However, this approach is expensive, and whether it actually enhances delivery to intended locations is debated. An alternative approach that sidesteps these issues, but requires creative chemistry, is to deliver drugs in carriers that fall apart in response to either biochemical characteristics of disease, such as the increased reactive oxygen species (ROS) levels found in inflamed tissues, or external stimuli, such as near infrared light. Near infrared (NIR) is an especially advantageous stimulus, as it safely penetrates more deeply than other wavelengths, and light allows precise spatiotemporal control. We have developed several polymers that enable such on-demand release through triggered depolymerization. Both NIR and the concentrations of ROS found in inflammation are relatively weak signals; NIR-induced cleavage requires simultaneous absorption of two photons, which limits the number of cleavage events, and inflammation only increases H2O2 concentrations to ~50 µM. Thus, translating these signals into drug release requires amplification. Our designs address this need both chemically, through self-immolative polymer backbones, and physically: nanoparticle formulation translates few cleavage events into pores allowing drug escape.