Nanogels have potential for encapsulating cancer therapeutics, yet their susceptibility to physiological degradation and lack of cellular specificity hinder their use as effective oral delivery vehicles. Herein, we engineered novel albumin-core with folic acid functionalized hyperbranched amylopectin shell-type nanogels, prepared through a two-step reaction and loaded with curcumin while the proteinaceous core was undergoing thermal gelation. The nanogels had a mean hydrodynamic diameter of ca. 90 nm and zeta-potential of ca. -24 mV. Encapsulation of curcumin within the nanogels was restored, up to ca. 0.05 mg mL(-1), beyond which, a gradual increase in size and a decrease in zeta-potential was observed. The core-shell structures were resilient to in vitro physiological oral-gastrointestinal digestion owing to a liquid crystalline B- and V-type polymorphism in the polysaccharide shell, the latter being driven by the shell functionalization with folic acid. Additionally, these biocompatible nanogels restored stability of the encapsulated curcumin and exhibited augmented cellular uptake and retention specifically in folate receptor-positive HT29 human colon adenocarcinoma cells, inducing early-stage apoptosis. Novel insights from this study represent a promising platform for rational designing of future oral delivery systems that can surmount physiological barriers for delivering cancer therapeutics to colon cancer cells with improved stability and specificity. (C) 2020 Elsevier Inc. All rights reserved.