The design of drug delivery systems capable of efficiently delivering poorly soluble drugs to target sites still remains a major challenge. Such materials require several different functionalities; typically, these materials should be biodegradable and nontoxic, non-immunogenic, responsive to their environment, and soluble in aqueous solution while retaining the ability to solubilize hydrophobic drugs. Here, we report on a polypeptide-polymer hybrid of elastin-like polypeptides (ELPs) and poly(2-oxazoline)s (POx). This paper describes the chemical synthesis, physical characteristics, and drug loading potential of these novel hybrid macromolecules. To this end, we introduce a novel method for terminal functionalization of POx with protected maleimide moieties. Following recovery of the maleimide group via a retro Diels-Alder reaction, the consecutive Michael addition of thiol-functionalized ELPs yielded the desired protein-polymer conjugate. These conjugates formed nanoparticles in aqueous solution capable of solubilizing the anti-cancer drug paclitaxel with up to 8 wt% loading.