title: Linoleic acid-grafted chitosan oligosaccharide micelles for intracellular drug delivery and reverse drug resistance of tumor cells.
abstract: Intracellular drug delivery is an important rout to reverse drug resistance of tumor cells. In this study, the linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) was synthesized to construct a micellar delivery system for intracellular delivery. The synthesized linoleic acid-grafted chitosan oligosaccharide (CSO-LA) with 10.3% graft ratio of LA could form micelles in aqueous with 86.69 μg/ml critical micellar concentration (CMC). The CSO-LA micelle had 46.2±3.6 nm number average diameter and 36.0±3.3 mV zeta potential. Taking doxorubicin base (DOX) as a model drug, the drug-loaded CSO-LA micelles (CSO-LA/DOX) was then prepared. The drug encapsulation efficiencies of CSO-LA/DOX were as high as 80%, and the drug loading capacity could be improved by increasing the charged DOX. Using MCF-7, Doxorubicin·HCl resistant MCF-7 (MCF-7/ADR), K562 and Doxorubicin·HCl resistant K562 (K562/ADR) cells as model drug sensitive and drug resistant tumor cells, the experiments demonstrated the CSO-LA had excellent cellular uptake ability by either drug sensitive tumor cells or drug resistance tumor cells. The CSO-LA micelles could deliver DOX into tumor cells, and the DOX in cells was increased with incubation time. As a result, the cytotoxicities of DOX encapsulated in CSO-LA micelles against drug resistance tumor cells were improved significantly, comparing to that of Doxorubicin·HCl solution.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China. duyongzhong@zju.edu.cn
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D019787:Linoleic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009844:Oligosaccharides / Q000737:chemistry*
chemical_list: D008823:Micelles; D009844:Oligosaccharides; D004317:Doxorubicin; D048271:Chitosan; D019787:Linoleic Acid