Aptamer mediated cytotoxicity of drug carrying silica nanoparticles

Aptamers are single stranded DNA or RNA molecules which have high affinity and specificity against their targets. Aptamer AS1411 targets nucleolin protein which is upregulated on cell surface of variety of cancer types. AS1411 aptamer capped MCM-41 mesoporous silica nanoparticles can be utilized as a targeted drug delivery system. This study aims to assess the targeting ability, localization, and cytotoxicity of drug loaded AS1411 aptamer capped MCM-41 type silica nanoparticles (Apta-NP) on nucleolin positive triple negative murine breast cancer cells, E0771. Capping of mesoporous silica nanoparticles with AS1411 aptamer inhibits drug release from pores of nanoparticle in closed conformation, when AS1411 aptamer interacts with its target, nucleolin, conformational change on aptamer structure induces drug release. In this study, in order to show cellular localization and uptake of Apta-NP drug delivery system, first, E0771 cells were treated with either fluorescein loaded Apta-NP (Apta-NP-Fl) delivery system or fluorescein loaded NP (NP-Fl). Increased uptake of fluorescein was measured in cells treated with Apta-NP-Fl in comparison to NP-Fl. Later, the same cell line was incubated with either paclitaxel loaded Apta-NP (Apta-NP-TXL) or free paclitaxel in range of 0-100 µM for 24 or 48 hours and cell viability was measured. IC50 values for free TXL and Apta-NP-TXL delivery system were 45.76 µM and 36.41 µM, respectively after 24 hours incubation while values were 48.87 µM and 35.64 µM after 48 hours incubation. Then, to examine in vivo targeting ability of Ap-NP system, E0771 cells were inoculated into right flank of C57bl/6 mice and localization of fluorescein cargo of Apta-NP delivery system was determined using in vivo fluorescence imaging technique. One hour after the injection, localization of fluorescence signal around tumor region was observed. 24 hours after injection, fluorescence signal was cleared off the body. Therefore, Apta-NP complex might be suggested as a good candidate for targeted breast cancer therapy in respect to lower IC50 value on murine breast cancer cell line and ability to localize on allograft breast cancer model.