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

• Published in: Macromolecular research 2018, 26(7), , pp.650-658
• Main Authors: Anh, Jun-Hyuk, Jeong, Gyeong-Won, Nah, Jae-Woon
• Format: Article
• Language: English
• Subjects: Anticancer properties; Cancer; Characterization and Evaluation of Materials; Chemical bonds; Chemistry; Chemistry and Materials Science; Chitosan; Complex Fluids and Microfluidics; Coupling (molecular); Coupling agents; Cytoplasm; Destabilization; Dialysis; Dismantling; Doxorubicin; Drug carriers; Drug delivery systems; Fluorescence; Glutathione; Lipoic acid; Low molecular weights; Morphology; Nanochemistry; Nanotechnology; Particle size; Physical Chemistry; Polymer Sciences; Soft and Granular Matter; Surface charge; Toxicity; 고분자공학
• ISSN: 1598-5032; 2092-7673
• DOI: 10.1007/s13233-018-6113-1

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 redox-responsive 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.