Propolis has well-known antimicrobial activity as well as antioxidant, antitumoral, anti-inflammatory, and regenerative properties, but its effects on the immune response are not well understood. Furthermore, clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility and, consequently, minimal systemic bioavailability. Nanoparticle-based delivery approaches have the potential to render hydrophobic agents like propolis dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. We have synthesized a polymeric nanoparticle-encapsulated formulation of propolis (propolis nanofood) utilizing micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM) with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol) monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50-nm range. Propolis nanofood, unlike free propolis, is readily dispersed in aqueous media. Propolis nanofood demonstrates comparable in vitro therapeutic efficacy to free propolis against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Future studies utilizing propolis nanofood are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of propolis.