In vitro and in vivo evaluation of sandwich-like mesoporous silica nanoflakes as promising anticancer drug delivery system

• Published in: International journal of pharmaceutics Vol. 506; no. 1-2; pp. 458 - 468
• Main Authors: Peruzynska, M., Szelag, S., Trzeciak, K., Kurzawski, M., Cendrowski, K., Barylak, M., Roginska, D., Piotrowska, K., Mijowska, E., Drozdzik, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2016
• Subjects: Animals; Anticancer drug delivery; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacokinetics; Antimetabolites, Antineoplastic - pharmacology; Breast Neoplasms - drug therapy; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Drug Delivery Systems; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Injections, Intravenous; Male; Melanoma - drug therapy; Mesoporous silica nanoflakes; Methotrexate - administration & dosage; Methotrexate - pharmacokinetics; Methotrexate - pharmacology; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomaterials biocompatibility; Nanostructures; Polyethylene Glycols - chemistry; Porosity; Silicon Dioxide - chemistry; Tissue Distribution; Nanomaterials biocompatibility; Mesoporous silica nanoflakes; Anticancer drug delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.03.041

[Display omitted] We present the new promising nanostructure- sandwich-like mesoporous silica nanoflakes synthesized on graphene oxide sheets core. In the first step biocompatibility of the nanoflakes with PEG and without functionalization in human fibroblast, melanoma and breast cancer cells was assessed. In order to define the cellular uptake in vitro and biodistribution in vivo the nanostructures were labelled with fluorescent dye. In the next step, the silica nanostructures were filled by the anticancer drug- methotrexate (MTX) and cytotoxicity of the complex in reference to MTX was evaluated. The WST-1 assay shows mild, but concentration dependent, cytotoxicity of the nanoflakes, most significant for the non-functionalized structures. PEG-modified silica nanoflakes didn’t produce a disruption of cell membranes and lactate dehydrogenase (LDH) release. Cell imaging revealed efficient internalization of the silica nanoflakes in cells. Ex vivo organ imaging showed high accumulation of the nanostructures in lungs, bladder and gall bladder, whereas confocal imaging revealed wide nanoflake distribution in all tested tissues, especially at 1h and 4h post intravenous injection. Cytotoxicity of the nanoflake-MTX complex in reference to MTX showed similar cytotoxic potential against cancer cells. These findings may provide useful information for designing drug delivery systems, which may improve anticancer efficacy and decrease side effects.