Hepatocellular carcinoma chemotherapy remains constrained by off-target toxicity and multidrug resistance, underscoring the need for biobased nanostructured carriers capable of tumor microenvironment-responsive drug delivery. Here, we report cyclodextrin-linked corn starch nanostructured microgels prepared by inverse water-in-oil emulsion crosslinking with epichlorohydrin as a sustainable platform for doxorubicin delivery. Systematic variation of the β-cyclodextrin content generated colloidally stable microgels with hydrodynamic diameters in the 215–410 nm range, narrow polydispersity indices (~0.22–0.31) and increasingly negative zeta potentials down to −21.5 mV. Nitrogen sorption, FTIR, XRD and thermal analyses confirmed the formation of mesoporous polymer networks, with the lead formulation (CS-CD-3) exhibiting a BET surface area of 12.45 m²/g and an average pore diameter of 9.8 nm. Doxorubicin loading into these microgels afforded high drug payloads with an encapsulation efficiency of 78.4% for CS-CD-3. In vitro release studies demonstrated pronounced pH-dependent behavior, with only ~24% cumulative release at physiological pH 7.4 versus ~72% at pH 5.0 after 24 h, consistent with the intrinsic pH-dependent ionization of doxorubicin and the associated pH-modulated DOX–β-cyclodextrin host–guest interactions within the microgel network. Kinetic fitting of the pH 5.0 release data (Higuchi and Korsmeyer–Peppas models) indicated diffusion through a hydrated matrix with an additional polymer-relaxation contribution under acidic in vitro conditions (n ≈ 0.62). Blank microgels preserved >90% cell viability in both HepG2 and L02 cells, whereas doxorubicin-loaded CS-CD-3 microgels decreased the IC50 in HepG2 cells from 2.15 ± 0.18 to 0.85 ± 0.12 μg/mL and increased the IC50 in L02 cells from 4.50 ± 0.35 to 8.20 ± 0.65 μg/mL, improving the selectivity index from 2.09 to 9.64. Confocal imaging confirmed efficient endocytic uptake, endo-lysosomal release and enhanced apoptotic nuclear damage. These results highlight nanostructured cyclodextrin–starch microgels as a promising bio-derived nanoplatform for safer, more selective hepatocellular carcinoma chemotherapy.
Wang et al. (Tue,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: