Precise control of the physical and biochemical properties of nanoparticle-based drug delivery vehicles is a prerequisite for effective transport of drugs across a range of biological barriers. To date, the range of biodegradable macromolecular systems with appropriate biocompatibility, low levels of immunogenicity and extended structural stability that can be prepared at scale remains rather limited. Towards that end, nanoparticles comprised of protein/polymer conjugates offer a range of unique features, such as biodegradability and extended in vivo stability, active targeting and stimuli-responsiveness, or the potential for delivery of small-molecule drugs and biopharmaceuticals. Electrohydrodynamic (EHD) co-jetting, an adaptive manufacturing process that involves transferring two or more capillary needles in a side-by-side configuration, can be used to create a wide range of multicompartmental protein/polymer nanoparticles. The protein nanoparticles combine the processability of synthetic polymers with the biological properties of proteins. In the context of glioblastoma multiforme, protein nanoparticles have been devised that enable systemic delivery of RNAi to intracranial brain tumors. Protein nanoparticles that can enable controlled release of combination drugs from the same nanoparticle will also be discussed.