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

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...

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Veröffentlicht in:Materials Science & Engineering C 2016-08, Vol.65, p.354-363
Hauptverfasser: Song, Meifang, Xue, Yanan, Chen, Lidi, Xia, Xiaoyang, Zhou, Yang, Liu, Lei, Yu, Bo, Long, Sihui, Huang, Shiwen, Yu, Faquan
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container_end_page 363
container_issue
container_start_page 354
container_title Materials Science & Engineering C
container_volume 65
creator Song, Meifang
Xue, Yanan
Chen, Lidi
Xia, Xiaoyang
Zhou, Yang
Liu, Lei
Yu, Bo
Long, Sihui
Huang, Shiwen
Yu, Faquan
description 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.
doi_str_mv 10.1016/j.msec.2016.04.029
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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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27157762</pmid><doi>10.1016/j.msec.2016.04.029</doi><tpages>10</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Alginates - chemistry
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Anticancer properties
Cell Survival - drug effects
Cercopithecus aethiops
Combinational stimulation
Controlled release
Doxorubicin - administration & dosage
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Carriers - chemistry
Effectiveness
Glucuronic Acid - chemistry
Glutathione - chemistry
HeLa Cells
Hep G2 Cells
Hexuronic Acids - chemistry
Human
Humans
Hydrogen-Ion Concentration
In vivo methods and tests
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Logic
Magnetics
Mice
Mice, Inbred BALB C
Mice, Nude
Microscopy, Confocal
Nanogel
Nanostructure
Particle Size
pH/reduction responsiveness
Polyethylene Glycols - chemistry
Polyethyleneimine - chemistry
Reduction
Spectroscopy, Fourier Transform Infrared
Superparamagnetism
Toxicity
Transplantation, Heterologous
Vero Cells
title Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel
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