title: 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-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.
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Song
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Lidi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Sihui
authors.initials: S
authors.lastname: Long
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Huang
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China. Electronic address: fyu@wit.edu.cn.
authors.forename: Faquan
authors.initials: F
authors.lastname: Yu
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006367:HeLa Cells; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D000080385:Nanogels; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014183:Transplantation, Heterologous; D014709:Vero Cells
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006603:Hexuronic Acids; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D020723:Glucuronic Acid; D011094:Polyethyleneimine; D005978:Glutathione
keywords: Combinational stimulation; Controlled release; Nanogel; Superparamagnetism; pH/reduction responsiveness