Self-Immolative Linear Polymers: Towards New Polymer Backbones and Biomedical Applications

摘要

In recent years, there has been significant interest in the development of new biodegradable and stimuli responsive polymers for biomedical applications. For example, polyesters such as poly(lactic acid)~1 and polycaprolactone~2 have been extensively used in tissue engineering, biomedical devices, and drug delivery applications while several pH~3 and thermosensitive~4 polymers have also been investigated. Inspired by work on their dendritic analogues,~(5,6) self-immolative linear polymers introduce a new combination of degradability and stimuli sensitivity.~(7-9) As illustrated in Figure 1, these polymers comprise a backbone that is stable in the presence of an end cap, but which upon removal of the end cap undergo a cascade of intramolecular reactions leading to complete depolymerization. By tuning the end caps to be cleaved in response to stimuli such as enzymes, photochemical irradiation, or changes in pH or redox potential, a single polymer backbone can be engineered to be degrade under different conditions. In addition, these materials should exhibit the property that the time required for degradation should be dependent on the length of the polymer. When incorporated into nanoparticles, polymer assemblies, or other biomedical materials, self-immolative polymers should allow for an unprecedented level of control over the biodegradation process allowing for the triggered release of drug molecules or the breakdown of other medical materials. Our group's progress towards the development of this unique class of molecules will be described here.