Abstract
Halloysites are cheap, abundantly available, and natural with high mechanical strength and biocompatibility. In this paper, a novel halloysite nanotube [HNT]-based gene delivery system was explored for loading and intracellular delivery of antisense oligodeoxynucleotides [ASODNs], in which functionalized HNTs [f-HNTs] were used as carriers and ASODNs as a therapeutic gene for targeting survivin. HNTs were firstly surface-modified with γ-aminopropyltriethoxysilane in order to facilitate further biofunctionalization. The f-HNTs and the assembled f-HNT-ASODN complexes were characterized by transmission electron microscopy [TEM], dynamic light scattering, UV-visible spectroscopy, and fluorescence spectrophotometry. The intracellular uptake and delivery efficiency of the complexes were effectively investigated by TEM, confocal microscopy, and flow cytometry. In vitro cytotoxicity studies of the complexes using MTT assay exhibited a significant enhancement in the cytotoxic capability. The results exhibited that f-HNT complexes could efficiently improve intracellular delivery and enhance antitumor activity of ASODNs by the nanotube carrier and could be used as novel promising vectors for gene therapy applications, which is attributed to their advantages over structures and features including a unique tubular structure, large aspect ratio, natural availability, rich functionality, good biocompatibility, and high mechanical strength.
Highlights
Gene therapy is attractive as a clinical treatment for cancers and genetic disorders
We developed a novel HNT-based drug delivery system containing ASODNs as a therapeutic gene for targeting survivin and functionalized HNTs [f-HNTs] as carriers
Cellular uptake of the f-HNT-ASODN complexes Transmission electron microscopy imaging assay HeLa cells were seeded at a density of 1 × 106 cells in a 60-mm tissue culture dish and grown overnight
Summary
Gene therapy is attractive as a clinical treatment for cancers and genetic disorders. Even though much less studied than carbon nanotubes, due to their interesting structure and features such as unique tubular structure, large aspect ratio, cheap and abundant availability, rich functionality, good biocompatibility, and high mechanical strength, HNTs are attractive materials that show great promise in a range of applications as a nanoscale container for the encapsulation of biologically active molecules (e.g., biocides, enzymes, and drugs), as a support for immobilization of catalyst molecules, controlled drug delivery, bioimplants, and for protective coating (e.g., anticorrosion or antimolding) [19,20,21,22,23] Despite these prospects, their utilization as biocarrier for ASODNs delivery has been less investigated so far. The results indicated that these natural, cheap, and abundantly available clay nanotubes could be used as novel vectors in the promising application of gene therapy
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