title: Gene delivery potential of biofunctional carbonate apatite nanoparticles in lungs.
abstract: Existing nonviral gene delivery systems to lungs are inefficient and associated with dose limiting toxicity in mammalian cells. Therefore, carbonate apatite (CO3Ap) nanoparticles were examined as an alternative strategy for effective gene delivery to the lungs. This study aimed to (1) assess the gene delivery efficiency of CO3Ap in vitro and in mouse lungs, (2) evaluate the cytotoxicity effect of CO3Ap/pDNA in vitro, and (3) characterize the CO3Ap/pDNA complex formulations. A significantly high level of reporter gene expression was detected from the lung cell line transfected with CO3Ap/pDNA complex prepared in both serum and serum-free medium. Cytotoxicity analysis revealed that the percentage of the viable cells treated with CO3Ap to be almost similar to the untreated cells. Characterization analyses showed that the CO3Ap/pDNA complexes are in a nanometer range with aggregated spherical structures and tended to be more negatively charged. In the lung of mice, highest level of transgene expression was observed when CO3Ap (8 μL) was complexed with 40 μg of pDNA at day 1 after administration. Although massive reduction of gene expression was seen beyond day 1 post administration, the level of expression remained significant throughout the study period.
authors.affiliation: Medical Genetics Laboratory, Clinical Genetics Unit, Faculty of Medicine and Health Sciences, UPM, 43400 Serdang, Selangor, Malaysia.
authors.forename: Suleiman Yusuf
authors.initials: SY
authors.lastname: Alhaji
authors.affiliation: Jeffry Cheah School of Medicine and Health Sciences, Monash University Malaysia, 46150 Bandar Sunway, Selangor, Malaysia.
authors.forename: Ezharul Houque
authors.initials: EH
authors.lastname: Chowdhury
authors.affiliation: Medical Genetics Laboratory, Clinical Genetics Unit, Faculty of Medicine and Health Sciences, UPM, 43400 Serdang, Selangor, Malaysia ; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, UPM, 43400 Serdang, Selangor, Malaysia ; Genetics & Regenerative Medicine Research Centre, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia.
authors.forename: Rozita
authors.initials: R
authors.lastname: Rosli
authors.affiliation: Molecular Pathology Research Group, Faculty of Pharmacy and Biotechnology, German University, New Cairo 11835, Egypt.
authors.forename: Fatma
authors.identifier: 0000-0003-4419-0064
authors.initials: F
authors.lastname: Hassan
authors.affiliation: Medical Genetics Laboratory, Clinical Genetics Unit, Faculty of Medicine and Health Sciences, UPM, 43400 Serdang, Selangor, Malaysia ; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, UPM, 43400 Serdang, Selangor, Malaysia ; Genetics & Regenerative Medicine Research Centre, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, UPM, 43400 Serdang, Selangor, Malaysia.
authors.forename: Syahril
authors.identifier: 0000-0003-2718-6266
authors.initials: S
authors.lastname: Abdullah
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry*; D016923:Cell Death; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D023282:Nuclease Protection Assays; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D014162:Transfection
chemical_list: D001031:Apatites; C030782:carboapatite; D004247:DNA; D008156:Luciferases