Anticancer Effect of Intracellular-Delivered Doxorubicin Using a Redox-Responsive LMWSC-g-Lipoic Acid Micelles

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Abstract

To induce a quick-drug release, lipoic acid (LA) was introduced to amine group of low molecular weight water-soluble chitosan (LMWSC) by coupling agent. The disulfide bond (-S-S-) of lipoyl group from LMWSC-grafted lipoic acid (LL) can response to glutathione (GSH) at cytoplasm with reducing environment, where LL can rapidly be disassembled via dissociation of disulfide bond (-S-S-) by GSH. The doxorubicin (DOX)-encapsulated LL (LLDOX) was prepared by dialysis method, which allowed quick release of DOX by destabilization of inner-hydrophobic core of LL when disulfide bond (-S-S-) was dissociated by GSH. To demonstrate a redoxresponsive release behavior of LLDOX, its drug release was accomplished under PBS buffer (pH 7.4) and GSH (10 mM) condition. In addition, the particle size and morphology of LL and LLDOX were respectively confirmed by DLS and TEM. The particle sizes of LL30% and LL60% were indicated as 268.8±30.9 and 308.1±11.9 nm, respectively. In addition, particle size of LLDOX was decreased more than that of LL. Also, surface charge of LLDOX was displayed to strong positive charge (LLDOX30%: 12.6±0.5 mV, LLDOX60%: 9.6±1.1 mV). Moreover, their morphological structure has a spherical shape. The cytotoxicity LL and LLDOX was confirmed by using MTT assay. Besides, to investigate the intracellular uptake of DOX from LLDOX against HeLa and AGS cell lines, fluorescence image was observed by using fluorescence microscopy. These results suggest that LL is an excellent as a drug carrier due to high anticancer effect by rapid drug release with redox-responsive effect.

Keywords

LMWSC lipoic acid redox-responsive glutathione anticancer effect 

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Copyright information

© The Polymer Society of Korea and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Polymer Science and EngineeringSunchon National UniversityJeonnamKorea

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