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

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-NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 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 IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/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.