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

[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 as...

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Bibliographic Details
Published in:International journal of pharmaceutics 2016-06, Vol.506 (1-2), p.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: Article
Language:English
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
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Summary:[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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2016.03.041