Mucin-16 aptamer directed targeted delivery of sunitinib using mesoporous silica nanoparticles

Abstract

Sunitinib is a multi targeted Tyrosine Kinase Inhibitors. Owing to the similarity between molecular pathology of renal cell carcinoma (RCC) and ovarian cancer, the approved first-line chemotherapeutic agent for RCC (sunitinib) may be effective to control/treat ovarian. However, the undesired toxicities of sunitinib may be a limiting factor for clinical application; therefore the development of novel targeted drug delivery systems (DDSs) seems to be are. Aims The purpose of this study was to synthesize mesoporous silica nanoparticles armed with mucin16 aptamer (against CA125) for targeted delivery of sunitinib to MUC-16 positive cells. Materials and methods Mesoporous silica nanoparticles were synthesized using sol-gel method and then PEGylated, then sunitinib was loaded into the pores. Afterward the surface was modified with MUC-16 aptamer. The physicochemical characteristics of nanoparticles were assessed by FT-IR, TEM and DLS. To evaluate the viability of OVCAR-3 and SK-OV-3 cell lines upon treatment with MSNP-PEG-SUN-MUC-16, MTT assay was performed. Finally, the uptake of nanoparticles was evaluated by Flow cytometry. Results Uniform and spherical MSNPs were synthesized, sunitinib and aptamer were loaded into the nanoparticles step by step. MSNPs suspensions showed a significantly different drug release at pH 5.4, 6.4, and 7.4. In biological assays, MSNP-PEG-SUN-MUC-16 showed the most toxicity in OVCAR-3 (positive cell line), however, in SK-OV-3 (negative ones) MSNP-PEG-SUN-MUC-16 and MSNP-PEG-SUN had somehow similar toxicities. The uptake of MSNP-PEG-SUN-MUC-16 is significantly greater in positive cells.

Discussion This study provided preliminary evidence that MUC-16 aptamer as a targeting agent could increase the toxicity of sunitinib in a positive cell line, and the prepared nanosystem could reduce side effects and increase the efficacy of the treatment. The uptake study showed a greater uptake of MUC-16-conjugated nanoparticles in OVVCAR-3. These results suggest that MSNP-PEG-SUN-MUC-16 could be a potential targeting agent at the cellular level.