title: Ursolic acid-loaded chitosan nanoparticles induce potent anti-angiogenesis in tumor.
abstract: Angiogenesis provides necessary nutrients and oxygen for tumor growth and metastasis; thus, every stage of angiogenesis process is the potential target for cancer therapies. Ursolic acid (UA) is reported to decrease tumor burden through anti-angiogenesis pathway, but its poor water solubility greatly limits its efficiency and clinical application. Here, a simple method for preparing UA-loaded chitosan nanoparticles (CH-UA-NPs) with anti-angiogenesis and anti-tumor activity was demonstrated. In vitro, CH-UA-NPs could significantly inhibit the proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs). After uptake by HUVECs, CH-UA-NPs were mainly localized in lysosomes and mitochondria, but not nuclei. CH-UA-NPs induced the destruction of lysosome membrane integrity, collapse of mitochondrial membrane potential, and reorganization of cell cytoskeleton. All these changes led to the apoptosis or necrosis in HUVECs. In vivo, CH-UA-NPs could inhibit the angiogenesis in chicken chorioallantoic membrane (CAM) model and H22 xenograft model. Notably, comparing with free UA, such synthesized CH-UA-NPs could save about tenfold of UA doses, implying that this could significantly decrease the side effects induced by high doses of UA in biological organism. Our data showed that CH-UA-NPs and this nanoparticle-based drug delivery system could be as a potential drug candidate for anti-angiogenesis treatment.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 000853, China.|Department of Microbiology and Immunology, University of Illinois, Chicago, 60612, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 000853, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Pi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 000853, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.affiliation: Qingpu District, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China.
authors.forename: Chaomin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Material Science Lab, SAE Technologies Development (Dongguan) Co. Ltd, Dongguan City, 523087, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Material Science Lab, SAE Technologies Development (Dongguan) Co. Ltd, Dongguan City, 523087, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, 60612, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 000853, China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 000853, China. tjycai@jnu.edu.cn.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, 60612, USA. zchen@uic.edu.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D048271:Chitosan / Q000737:chemistry*; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D004337:Drug Carriers / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000517:prevention & control*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D020533:Angiogenesis Inhibitors; D048271:Chitosan; D004337:Drug Carriers; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Anti-angiogenesis; Anti-tumor activity; Chicken chorioallantoic membrane model; H22 xenografts mouse model; Ursolic acid-loaded chitosan nanoparticles