Silica nanowires conduct drugs into cells

The research details the use of silica nanowires (NW) that are 50,000 times smaller in diameter than a human hair as delivery vehicles for the Escherichia coli​ (E. coli​) Shiga toxin 1 A subunit into both human and bovine cells. The research, conducted by researchers form the University of Idaho, US and the Seoul National University in Korea, has been published as an early view article in the journal Nano Letters​.​ According to the authors, there is a great interest in developing nanomaterials to deliver therapeutic agents to cells as their size may permit them to carry drugs across physiological barriers such as the blood-brain-barrier, the branching pulmonary pathway and the tight epithelial junctions that can impede drug delivery and targeting. The authors write that: "the potential uses of this technology include immunotherapy for various diseases such as cancer, autoimmunity, or infectious diseases."​ The surfaces of nanowires can also be functionalised to promote targeting, biocompatibility, solubility and controlled drug release - enabling drugs to be delivered to specific cells at lower doses and reduced toxicity. The researchers coated the nanowires with fibronectin (Fn) to encourage the internalisation of the nanowires by cells and used them to deliver a recombinant Shiga toxin type 1 (Stx1) A subunit (StxA1) into cultured human laryngeal epithelial cells (HEp-2) and bovine mammary epithelial MAC-T cells. "We used recombinant StxA1 which cannot naturally enter cells without its counterpart B subunits,"​ write the authors. The nanowires were characterised using X-ray photoelectron spectroscopy (XPS) before studying the assaying the effects they had on cells. Using a neutral red cytoxicity assay the researchers determined that while most cells treated with uncoated nanowires and those only functionalised with Fn were viable, those treated with NW-Fn-StxA1 suffered significant cytotoxicity and cell death. The assay also showed that the HEp-2 cells were more sensitive to the NW-Fn-StxA1 than the MAC-T cells. Various microscopy studies using optical microscopy, field emission electron microscopy, secondary electron imaging and backscattering electron imaging which showed that the morphology of the HEp-2 cells was more affected by the NW-Fn-StxA1 complexes than the MAC-T cells, with the authors suggesting that: "the reduced cytoxicity toward the MAC-T cells is due to hindered internalisation of NW-Fn-StxA1 complexes by endogenously expressed Fn." ​ Unlike HEp-2 cells, which are noted for their lack of Fn expression, MAC-T cells produce significant amounts of Fn that could compete with the NW-Fn-StxA1 complexes for a limited number of integrin sites on the cell surface. The researchers are continuing their studies to try to improve the internalisation of the nanowires as well as incorporating ligands that will target specific target cells.