title: Bioactive Core-Shell Nanofiber Hybrid Scaffold for Efficient Suicide Gene Transfection and Subsequent Time Resolved Delivery of Prodrug for Anticancer Therapy.
abstract: Nanofiber scaffold's ability to foster seemingly nonexistent interface with the cells enables them to effectively deliver various bioactive molecules to cells in the vicinity. Among such bioactive molecules, therapeutically active nucleic acid has been the most common candidate. In spite of such magnanimous efforts in this field, it remains a paradox that suicide gene delivery by nanofibers has never been sought for anticancer application. To investigate such a possibility, in the present work, a composite core-shell nanofiberous scaffold has been realized which could efficiently transfect suicide gene into cancer cells and simultaneously deliver prodrug, 5-Fluorocytosine (5-FC) in a controlled and sustained manner. The scaffold's ability to instigate apoptosis by suicide gene therapy in nonsmall lung cancer cells (A549) was ascertained at both phenotypic and genotypic levels. A cascade of events starting from suicide gene polyplex release from nanofibers, transfection, and expression of cytosine deaminase-uracil phosphoribosyltransferase (CD::UPRT) suicide gene by A549; subsequent prodrug release; and its metabolic conversion into toxic intermediates which finally culminates in host cells apoptosis has been monitored in a time-dependent manner. This work opens up new application avenues for nanofiber-based scaffolds which can effectively manage cancer prognosis.
authors.affiliation: Nanobiotechnology Laboratory, Centre for Nanotechnology, ‡Department of Biotechnology, Indian Institute of Technology Roorkee , Roorkee, Uttarakhand-247667, India.
authors.forename: Uday Kumar
authors.initials: UK
authors.lastname: Sukumar
authors.affiliation: Nanobiotechnology Laboratory, Centre for Nanotechnology, ‡Department of Biotechnology, Indian Institute of Technology Roorkee , Roorkee, Uttarakhand-247667, India.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Packirisamy
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D043525:Cytosine Deaminase / Q000235:genetics*; D005437:Flucytosine / Q000737:chemistry / Q000633:toxicity; D041722:Genes, Transgenic, Suicide; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D057139:Nanofibers / Q000737:chemistry*; D010430:Pentosyltransferases / Q000235:genetics*; D011355:Prodrugs / Q000737:chemistry* / Q000633:toxicity; D012235:Rhodamines / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D012235:Rhodamines; D005437:Flucytosine; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase; C029773:rhodamine B
keywords: anticancer therapy; core−shell nanofibers; gene transfection; prodrug; suicide gene