title: Folate-Chitosan Nanoparticles Loaded with Ursolic Acid Confer Anti-Breast Cancer Activities in vitro and in vivo.
abstract: Ursolic acid (UA) has proved to have broad-spectrum anti-tumor effects, but its poor water solubility and incompetent targeting property largely limit its clinical application and efficiency. Here, we synthesized a nanoparticle-based drug carrier composed of chitosan, UA and folate (FA-CS-UA-NPs) and demonstrated that FA-CS-UA-NPs could effectively diminish off-target effects and increase local drug concentrations of UA. Using MCF-7 cells as in vitro model for anti-cancer mechanistic studies, we found that FA-CS-UA-NPs could be easily internalized by cancer cells through a folate receptor-mediated endocytic pathway. FA-CS-UA-NPs entered into lysosome, destructed the permeability of lysosomal membrane, and then got released from lysosomes. Subsequently, FA-CS-UA-NPs localized into mitochondria but not nuclei. The prolonged retention of FA-CS-UA-NPs in mitochondria induced overproduction of ROS and destruction of mitochondrial membrane potential, and resulted in the irreversible apoptosis in cancer cells. In vivo experiments showed that FA-CS-UA-NPs could significantly reduce breast cancer burden in MCF-7 xenograft mouse model. These results suggested that FA-CS-UA-NPs could further be explored as an anti-cancer drug candidate and that our approach might provide a platform to develop novel anti-cancer drug delivery system.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, 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, 999078, 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, 999078, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Jiang
authors.affiliation: The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemistry, materials science and engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Bai
authors.affiliation: The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Mingtao
authors.initials: M
authors.lastname: Shao
authors.affiliation: Treatment and Research Center of Infectious Diseases, the 302 Hospital of PLA, Beijing, 100039, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Chemistry, materials science and engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, materials science and engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Peihui
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Chemistry, materials science and engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, China.|Department of Chemistry, materials science and engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago 60612, USA.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D014315:Triterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D048271:Chitosan; D005492:Folic Acid; D014315:Triterpenes; D000097245:Ursolic Acid