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Mesoporous lipid-silica nanohybrids for folate-targeted drug-resistant ovarian cancer

Abstract

Folic acid (FA) targets cancer by exploiting its overexpression of folic acid receptors (FR). A novel folate conjugated lipid coated mesoporous silica nanoparticle has been synthesized in this study to enhance cellular uptake and cytotoxicity and reduce multidrug resistance (MDR) in cancer. Mesoporous silica nanoparticles (MSN) have a high loading capacity of Doxorubicin (DOX) (0.012 mg mg1) due to its high surface to volume ratio. On coating these nanoparticles (DOX:MSN) with a lipid composition of DPPC:Cholesterol:DSPE-PEG2000:DSPE-PEG2000(folate) (DOX:FLMSN), a pH dependent sustained release property is achieved (~20% to ~97% between pH 7.4-4.5 after 168h of drug release). The system’s cellular uptake efficiency has been characterized against A2780S, A2780-Cis-Res (showing FR overexpression) and PC3 cells (lacking FR overexpression). DOX:FLMSN show significant improvement in cellular uptake in A2780S and A2780-Cis-Res but not in PC3 cells due to FR under-expression in the latter. However, in an FA saturated media, the improvement is neutralized due to receptor blocking by free FA. Cytotoxicity studies confirm the enhanced cell growth inhibition of DOX:FLMSN over free DOX and DOX:LMSN in both A2780S and A2780-Cis-Res cells thereby ameliorating MDR. Therefore, FA introduces active targeting in FR overexpressing cancer simultaneously disrupting MDR. The nanoformulation DOX:FLMSN can be further investigated in vivo.

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Supplementary files

Publication details

The article was received on 06 Sep 2017, accepted on 10 Jan 2018 and first published on 12 Jan 2018


Article type: Paper
DOI: 10.1039/C7NJ03334F
Citation: New J. Chem., 2018, Accepted Manuscript
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    Mesoporous lipid-silica nanohybrids for folate-targeted drug-resistant ovarian cancer

    S. Samanta, L. Pradhan and D. Bahadur, New J. Chem., 2018, Accepted Manuscript , DOI: 10.1039/C7NJ03334F

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