(229ag) Polyacetal As a Novel Drug Carrier for Targeted Cancer Therapies

There has been an increasing focus in modern cancer research on the development of materials that can efficiently deliver therapeutics to a pre-identified solid tumor target. Due to their unique properties, stimuli responsive polymers (SRPs) have been of particular interest. One such SRP is a polyacetal-based copolymer (PAC). PAC shows both remarkable temperature response that is linearly dependent on composition and pH dependent degradation properties at physiological pH ranges; making it one of the most desirable materials for targeted cancer therapy. Here, we discuss the fundamental origins of the lower critical solution temperature (LCST) behavior, exhibited by this polymer. Our results indicate that the observed LCST scales linearly with the number of carbon and oxygen atoms in the polymer repeat units, allowing for precise control over the LCST. Furthermore, due to its unique pH dependent breakdown mechanism, the molecular purity of the encapsulated drug is retained post degradation. Therefore, we design PAC to include cancer therapeutics in its polymer-backbone, utilizing strategies to modify step-growth polymerization to obtain, for the first time, temperature-responsive main-chain drug conjugates. The temperature response in these main-chain drug conjugates allow for effective delivery of therapeutics to the tumor site, followed by acid-hydrolysis in acidic local tumor environments, to release pristine drug-molecules directly at the tumor site. These results strongly suggest that PAC possess both active targeting and degradation mechanisms that will greatly enhance the design of drug delivery vehicles.