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Life sciences · Journal article
Scientific Reports · September 26, 2026
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Abstract Smart nanogels, combining hydrogel and nanomaterial features, are promising drug carriers for cancer therapy because they can release cargo in response to tumor-related conditions. This study presents an easy, rapid synthesis of exceptionally small nanogels. To our knowledge, this is the first report of redox-degradable, multi-stimuli-responsive nanogels with relatively uniform size distributions, exhibiting a Z-average hydrodynamic diameter of 19.1 ± 0.3 nm in the collapsed state at 65 °C and a dry-state TEM diameter of 26 ± 6 nm, produced by aqueous nanogel-forming polymerization conducted entirely at room temperature without surfactants or organic solvents. The nanogels were synthesized by semi-batch radical polymerization of N-isopropylacrylamide (NIPA) using the redox-sensitive cross-linker N, N′-diacryloyl-L-cystine disodium salt (DACS), prepared in-house. DACS introduced COO⁻ groups, providing pH sensitivity, colloidal stability, and the ability to bind epirubicin hydrochloride (EPB). DLS and TEM revealed GSH concentration-dependent changes in nanogel size and morphology consistent with reductively induced structural disintegration. Drug-release studies showed minimal EPB release at pH 7.4, whereas the highest release was observed at pH 5.0 in the presence of 40 mM GSH, a strongly reducing condition used to accelerate nanogel disintegration. The nanogels showed relatively high drug loading (~ 33%). EPB-loaded nanogels retained cytotoxic activity toward MCF-7 cancer cells while showing lower cytotoxicity than free EPB toward non-tumorigenic MCF-10 A cells. In vivo, the EPB-loaded nanogels produced promising but heterogeneous tumor-suppressive effects, accompanied by necrosis and fibrotic tissue remodeling. These findings provide preliminary evidence of antitumor activity, although spontaneous regression in some untreated animals and inter-animal variability indicate that further validation is required.