title: A nanoparticle formula for delivering siRNA or miRNAs to tumor cells in cell culture and in vivo.
abstract: To improve RNA delivery, we present a protocol to produce an RNA carrier based on a Zn(II)-dipicolylamine (Zn-DPA) analog, which is an artificial receptor for phosphate anion derivatives. We further functionalized this Zn-DPA analog to hyaluronic acid (HA)-based self-assembled nanoparticles (HA-NPs) with a hydrodynamic diameter of 100 nm by conjugating amine-functionalized Zn-DPA molecules onto the HA-NPs through amide formation, resulting in efficient tumor-targeted delivery of RNAs (siRNAs, miRNA or other short oligoribonucleotides) and small-molecule drugs. The functional group of Zn-DPA can be converted into other groups such as a carboxylic or thiol group, and the DPA analog can be covalently attached to a variety of existing and novel platforms or formulations for the development of multifunctional materials via standard bioconjugation techniques. Protocols for RNA formulation and delivery into tumor tissues and tumor cells are also described. Our design strategy offers a versatile and practical method for delivering both RNA and chemotherapeutics to tumor cells and expands existing nanomaterial capabilities to further the field of drug and gene delivery.
authors.affiliation: 1] Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA. [2] Department of Chemical Engineering and the David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3].
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.affiliation: 1] Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA. [2].
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Silvestre
authors.affiliation: 1] Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA. [2].
authors.forename: Xinglu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hida
authors.affiliation: 1] Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA. [2] Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Fujian, Xiamen, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Don N
authors.initials: DN
authors.lastname: Ho
authors.affiliation: 1] Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA. [2] Department of Radiology, the Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Korea.
authors.forename: Jong In
authors.initials: JI
authors.lastname: Hong
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008819:Mice, Nude; D035683:MicroRNAs; D053758:Nanoparticles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010847:Picolines / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D035683:MicroRNAs; D009942:Organometallic Compounds; D010847:Picolines; D034741:RNA, Small Interfering; C509592:zinc(II) dipicolylamine; D006820:Hyaluronic Acid