Polyethylene glycol-decorated doxorubicin/carboxymethyl chitosan/gold nanocomplex for reducing drug efflux in cancer cells and extending circulation in blood stream
- Authors
- Kang, Jin-Wook; Cho, Hyun-Jong; Lee, Hyo Jung; Jin, Hyo-Eon; Maeng, Han-Joo
- Issue Date
- Mar-2019
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Carboxymethyl chitosan; Gold nanoparticle; Doxorubicin; PEGylation; Multidrug resistance overcoming; Prolonged circulation
- Citation
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, v.125, pp.61 - 71
- Journal Title
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
- Volume
- 125
- Start Page
- 61
- End Page
- 71
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/1723
- DOI
- 10.1016/j.ijbiomac.2018.12.028
- ISSN
- 0141-8130
- Abstract
- Polyethylene glycol (PEG)-decorated doxorubicin (Dox)/carboxymethyl chitosan (CMC)/gold nanoparticles (AuNPs) have been developed for cancer therapy. CMC was used as a reducing and stabilizing agent for the fabrication of AuNPs and Dox was loaded onto AuNPs as a chemotherapeutic agent. Dox-loaded CMC-stabilized AuNPs (Dox/CMC-AuNPs) with a mean diameter of 104.0 nm, zeta potential of -4832 my, and drug loading efficiency of 60.14% were prepared. PEG was attached to CMC-AuNPs for enhancing systemic drug exposure and prolonging the circulation in blood stream. Compared with Dox/CMC-AuNPs, Dox-loaded PEGylated CMCAuNPs (Dox/CMC-AuNPs-PEG) showed a reduced hydrodynamic size (71.2 nm), less negative zeta potential (-12.83 mV), and an enhanced Dox loading efficiency (73.14%). Dox/CMC-AuNPs and Dox/CMC-AuNPs-PEG exhibited sustained and pH-dependent drug release profiles and exhibited antiproliferation effects against the A549 cells. In a bi-directional transport study of Caco-2 cell monolayers, AuNPs reduced the efflux ratio, which indicated that the P-glycoprotein-mediated multidrug resistance (MDR) was overcome. Dox/CMC-AuNPs-PEG resulted in reduced drug clearance (CL) and improved half-life (t(1/2)), compared with Dox/CMC-AuNPs, in rats after intravenous administration. These results suggest that Dox/CMC-AuNPs-PEG could be a promising nanotherapeutic approach to overcome MDR in cancer and prolong their circulation in the blood stream. (C) 2018 Elsevier B.V. All rights reserved.
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