Mucin-16 aptamer directed targeted delivery of Erlotinib using PEGylated magnetic nanoparticles

Abstract

Erlotinib (ERL) is a FDA-approved small-molecule tyrosine kinase inhibitor, but the undesired toxicities of ERL may be a limiting factor for clinical application in cancer patients; therefore, the development of novel targeted drug delivery systems (DDSs) seems to be advantageous. Aims The purpose of this study was to synthesize magnetic nanoparticles (MNPs) armed with mucin-16 aptamer (against cancer antigen 125) for targeted delivery of erlotinib to MUC-16 positive and negative ovarian cancer cell lines. Materials and methods The physicochemical characteristics and structure of synthesized nanoparticles were assessed by FT-IR, TEM, DLS, and VSM analyses. To evaluate the viability of OVCAR-3 and SK-OV-3 cell lines upon treatment with targeted erlotinib loaded MNPs, MTT assay was performed. Also, the uptake of nanoparticles was evaluated by Flow cytometry. Finally, the study of apoptosis and necrosis of treated cells was conducted. Results MNPs suspension showed a significantly different drug release at pH 5.4, 6.4, and 7.4. In biological assays, MUC16 armed MNPs showed the most toxicity in OVCAR-3 (positive cell line), however, in SK-OV-3 (negative ones) ERL-SPION-Val-PEG and ERL-SPION-Val-PEG-MUC16 had somehow similar toxicities. The uptake of ERL-SPION-Val-PEG-MUC16 in OVCAR-3 cells is significantly greater than its uptake in SK-OV-3 cells. Moreover, the level of cell apoptosis upon treatment by ERL-SPION-Val-PEG-MUC16 was higher in OVCAR-3 cell line compared to SK-OV-3. Discussion magnetic nanoparticles were spherical and their average diameter was about 63.40 nm with surface charge of –7.1 mV. The uptake study showed that the uptake of MUC16-conjugated nanoparticles was considerably increased in mucin-16 positive cell line. This study provided preliminary evidence that prepared nano-system could effectively deliver drug to the ovarian cancer cells and MUC16 aptamer as targeting agent could increase the toxicity of chemotherapeutic agent in positive cell line which was corroborated by the results of apoptosis and necrosis study.