Thermoresponsive Self-Immolative Polyglyoxylamides

Abstract

Thermo-responsive polymers with lower critical solution temperatures (LCSTs) are of significant interest for a wide range of applications from sensors to drug delivery vehicles. However, the most widely investigated LCST polymers have non-degradable backbones, limiting their applications in vivo or in the environment. Described here are thermo-responsive polymers based on a self-immolative polyglyoxylamide (PGAM) backbone. Poly(ethyl glyoxylate) was amidated with six different alkoxyalkyl amines to afford the corresponding PGAMs and their cloud point temperatures (Tcps) were studied in water and buffer. Selected examples with promising thermo-responsive behavior were also studied in cell culture media and their aggregation behaviour was investigated using dynamic light scattering (DLS). The Tcps were effectively tuned by varying the pendent functional groups. These polymers depolymerized end-to-end following the cleavage of end-caps from their termini. The structures and aggregation behavior of the polymers influenced their rates of depolymerization, and in turn the depolymerization influenced their Tcp. Cell culture experiments indicated that the polymers exhibited low toxicity to C2C12 mouse myoblast cells. This interplay between LCST and depolymerization behaviour, combined with low toxicity, make this new class of polymers of particular interest for biomedical applications.