title: Surface modification of PLGA nanoparticles with biotinylated chitosan for the sustained in vitro release and the enhanced cytotoxicity of epirubicin.
abstract: In this study, poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) with biotinylated chitosan (Bio-CS)-surface modification were prepared to be usded as a tumor-targeted and prolonged delivery system for anticancer drugs. Epirubicin (EPB), as a model drug, was encapsulated into Bio-CS surface modified PLGA (Bio-CS-PLGA) NPs with a drug encapsulation efficiency of 84.1 ± 3.4%. EPB-loaded Bio-CS-PLGA NPs were spherical shaped, and had a larger size and higher positive zeta potential compared to the unmodfied EPB-loaded PLGA NPs. The in vitro drug releases showed that EPB-loaded Bio-CS-PLGA NPs exhibited relatively constant drug release kinetics during the first 48 h and the drug burst release significantly decreased in comparison to the unmodified PLGA NPs. The results of MTS assays showed that Bio-CS-PLGA NPs markedly increased the cytotoxicity of EPB, compared to both the unmodified PLGA NPs and the CS-PLGA NPs. The uptakes of NPs in human breast cancer MCF-7 cells were evaluated by the flow cytometry and the confocal microscope. The results revealed that Bio-CS-PLGA NPs exhibited a greater extent of cellular uptake than the unmodified PLGA NPs and CS-PLGA NPs. Moreover, the cellular uptake of Bio-CS-PLGA NPs was evidently inhibited by the endocytic inhibitors and the receptor ligand, indicating that biotin receptor-mediated endocytosis was perhaps involved in the cell entry of Bio-CS-PLGA NPs. In MCF-7 tumor-bearing nude mice, EPB-loaded Bio-CS-PLGA NPs were efficiently accumulated in the tumors. In summary, Bio-CS-PLGA NPs displayed great potential for application as the carriers of anticancer drugs.
authors.affiliation: School of Life Science and Technology, The Key Laboratory of Biomedical Material, Xinxiang Medical University, Xinxiang, China. Electronic address: chenhlhl@126.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, The Key Laboratory of Biomedical Material, Xinxiang Medical University, Xinxiang, China.
authors.forename: Li Qin
authors.initials: LQ
authors.lastname: Xie
authors.affiliation: School of Life Science and Technology, The Key Laboratory of Biomedical Material, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Qin
authors.affiliation: School of Life Science and Technology, The Key Laboratory of Biomedical Material, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Jia
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Cai
authors.affiliation: School of Life Science and Technology, The Key Laboratory of Biomedical Material, Xinxiang Medical University, Xinxiang, China.
authors.forename: WenBin
authors.initials: W
authors.lastname: Nan
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China. Electronic address: wyang06@uic.edu.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Qi Qing
authors.initials: QQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019921:Biotinylation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002232:Carbocyanines / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004705:Endocytosis; D015251:Epirubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015251:Epirubicin; D048271:Chitosan
keywords: Biotin; Chitosan; Epbrubicin; PLGA nanoparticle