title: Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer.
abstract: Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene Bcl-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-1 signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, PR China; College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Deng
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Cao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, PR China; Key Laboratory of Pesticide Chemistry and Application, MOA, Institute of Plant Protection, CAAS, Beijing 100194, PR China.
authors.forename: Jiakun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, PR China; College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Kelei
authors.initials: K
authors.lastname: Hu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Yin
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Xiao
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China. Electronic address: shengwang@bjut.edu.cn.
authors.forename: Wang
authors.initials: W
authors.lastname: Sheng
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, PR China. Electronic address: wuy@nanoctr.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing 100124, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008027:Light; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects; D012542:Scattering, Radiation; D012997:Solvents; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D012997:Solvents; D004317:Doxorubicin; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Co-delivery; Combined therapy; Doxorubicin; MicroRNA-34a; Nanoparticles