Acid and reduction stimulated logic "and"-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel

Abstract A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH 2 ) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7 ± 20.3 nm in size with superparamagnetism. The combinational conditions of pH 5.0/10 mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH 7.4/10 mM (GSH) or pH 5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC 50 of 1.01 μg/mL and the human hepatoma cells (HepG2) with IC 50 of 1.57 μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy.