title: Folate mediated self-assembled phytosterol-alginate nanoparticles for targeted intracellular anticancer drug delivery.
abstract: Self-assembled core/shell nanoparticles (NPs) were synthesized from water-soluble alginate substituted by hydrophobic phytosterols. Folate, a cancer-cell-specific ligand, was conjugated to the phytosterol-alginate (PA) NPs for targeting folate-receptor-overexpressing cancer cells. The physicochemical properties of folate-phytosterol-alginate (FPA) NPs were characterized by nuclear magnetic resonance, transmission electron microscopy, dynamic light scattering, electrophoretic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug, was entrapped inside prepared NPs by dialysis method. The identification of prepared FPA NPs to folate-receptor-overexpressing cancer cells (KB cells) was confirmed by cytotoxicity and folate competition assays. Compared to the pure DOX and DOX/PA NPs, the DOX/FPA NPs had lower IC50 value to KB cells because of folate-receptor-mediated endocytosis process and the cytotoxicity of DOX/FPA NPs to KB cells could be competitively inhibited by free folate. The cellular uptake and internalization of pure DOX and DOX/FPA NPs was confirmed by confocal laser scanning microscopy image and the higher intracellular uptake of drug for DOX/FPA NPs over pure DOX was observed. The FPA NPs had the potential as a promising carrier to target drugs to cancer cells overexpressing folate receptors and avoid cytotoxicity to normal tissues.
authors.affiliation: College of Life Science, Anhui Normal University, Wuhu, 241000, PR China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Wang
authors.affiliation: Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241002, PR China; Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu, 241002, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Science, Wuhan, 430062, PR China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: College of Life Science, Anhui Normal University, Wuhu, 241000, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu, 241002, PR China.
authors.forename: Yafan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu, 241002, PR China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu, 241002, PR China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Xie
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Science, Wuhan, 430062, PR China. Electronic address: hfh.oilcrops@163.com.
authors.forename: Fenghong
authors.initials: F
authors.lastname: Huang
authors.affiliation: College of Life Science, Anhui Normal University, Wuhu, 241000, PR China. Electronic address: rmgong.nju@163.com.
authors.forename: Renmin
authors.initials: R
authors.lastname: Gong
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007624:KB Cells; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010840:Phytosterols / Q000737:chemistry*
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006603:Hexuronic Acids; D010840:Phytosterols; D004317:Doxorubicin; D020723:Glucuronic Acid; D005492:Folic Acid
keywords: Anticancer drug; Folate receptor; Phytosterol; Self-assembled nanoparticles; Targeted delivery