Polyacetals: Water-Soluble, pH-Degradable Polymers with Extraordinary Temperature Response

Temperature-responsive polymers exhibit a drastic change in solubility upon change in temperature, a property responsible for their increased use in a wide variety of emerging smart material applications. Here, we describe a flexible new family of polyacetals with lower critical solution temperature (LCST) behavior, falling out of aqueous solution upon increase in temperature. These are the first synthetic LCST polymers to be intrinsically biodegradable, forming neutral degradation products in acidic environments. The temperature response of the polyacetals is extraordinary. Their LCST cloud point temperatures can be predicted and tuned to high precision over a temperature range of ca. 6–80 °C as they are linearly dependent on the number of methylene and ethylene oxide units in the diol and divinyl ether monomers. We further demonstrate that the LCST temperatures are insensitive to salt and/or polymer concentration, properties that are important to in vivo applications, and that they are biocompatible.