Enhanced anticancer efficacy of epirubicin-loaded mesoporous silica nanocarriers through co-deliveryof an antimiR-۲۱ expressing plasmid to target colonadenocarcinoma in vitro and in vivo

Background: Cancer chemotherapy faces two main limitationsincluding severe side effects and drug resistance. Novel methodsin targeted drug delivery have established biocompatiblenanocarriers, which can increase the efficacy of chemotherapyin combination with gene therapy, while reducing the side effects.Since overexpression of miR-۲۱ and its association withepirubicin(EPI)-induced resistance is involved in colorectalcancer (CRC) progression, using efficient targeted nanocarriersto overcome drug resistance by miR-۲۱ inhibition seems apromising approach.Materials and Methods: In this study, we first designed andsynthesized mesoporous silica nanoparticles (MSNs) as thebackbone of the drug delivery system (DDS). After equippingMSNs with EPI as anticancer drug and antimiR-۲۱ expressingplasmid, the DDS was PEGylated and armed with AS۱۴۱۱ aptamerfor active targeting of CRC cells. The prepared nanocarrierswere fully characterized in terms of size and morphologicalproperties as well as elemental composition. Encapsulation andrelease of EPI and pDNA were investigated by spectrophotometryand gel electrophoresis, respectively. To estimate PEGylationinfluence on biocompatibility improvement, hemolysis assaywas performed. Afterwards, anticancer synergistic effectswere investigated with MTT assay and apoptosis measurement.Moreover, cellular uptake and transfection efficacy were comparedin C۲۶ colorectal cancer cells and NIH/۳T۳ as a normalcell line.Results: Successful production of the DDS with a mean diameterless than ۷۰ nm was demonstrated by physicochemicalcharacterization results; and loading content (LC) of EPI andpDNA was indicated as ۲۵ and ۱۰%, respectively. Hemolysisresults confirmed the biocompatibility of nanocarriers, and thesynergistic cytotoxicity and uptake of targeted formulation wassignificantly higher in C۲۶ cells compared to nucleolin negativeNIH/۳T۳ cells.Conclusion: According to the results, the targeted biocompatibleDDS combining chemo and gene therapy could stronglyenhance the anticancer properties of epirubicin, while reducingits side effects.

کلیدواژه ها:

Colorectal cancer ، Targeted therapy ، Gene therapy ، Epirubicin ، miR-۲۱