Fabrication of mesoporous silica nanoparticles for targeted delivery of sunitinib to ovarian cancer cells

Mitra Torabi; Ayuob Aghanejad; Pouria Savadi; Abolfazl Barzegari; Yadollah Omidi; Jaleh Barar

doi:10.34172/bi.2023.25298

Fabrication of mesoporous silica nanoparticles for targeted delivery of sunitinib to ovarian cancer cells

Bioimpacts. 2023;13(3):255-267. doi: 10.34172/bi.2023.25298. Epub 2023 Jan 23.

Authors

Mitra Torabi^{1

2}, Ayuob Aghanejad¹, Pouria Savadi³, Abolfazl Barzegari¹, Yadollah Omidi⁴, Jaleh Barar⁴

Affiliations

¹ Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
² Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
³ Di.S.T.A.Bi.F., University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100 Caserta, Italy.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Abstract

Introduction: Mesoporous silica nanoparticles (MSNPs) are considered innovative multifunctional structures for targeted drug delivery owing to their outstanding physicochemical characteristics.

Methods: MSNPs were fabricated using the sol-gel method, and polyethylene glycol-600 (PEG₆₀₀) was used for MSNPs modification. Subsequently, sunitinib (SUN) was loaded into the MSNPs, MSNP-PEG and MSNP-PEG/SUN were grafted with mucin 16 (MUC16) aptamers. The nanosystems (NSs) were characterized using FT-IR, TEM, SEM, DLS, XRD, BJH, and BET. Furthermore, the biological impacts of MSNPs were evaluated on the ovarian cancer cells by MTT assay and flow cytometry analysis.

Results: The results revealed that the MSNPs have a spherical shape with an average dimension, pore size, and surface area of 56.10 nm, 2.488 nm, and 148.08 m²g^-1, respectively. The cell viability results showed higher toxicity of targeted MSNPs in MUC16 overexpressing OVCAR-3 cells as compared to the SK-OV-3 cells; that was further confirmed by the cellular uptake results. The cell cycle analysis exhibited that the induction of sub-G1 phase arrest mostly occurred in MSNP-PEG/SUN-MUC16 treated OVCAR-3 cells and MSNP-PEG/SUN treated SK-OV-3 cells. DAPI staining showed apoptosis induction upon exposure to targeted MSNP in MUC16 positive OVCAR-3 cells.

Conclusion: According to our results, the engineered NSs could be considered an effective multifunctional targeted drug delivery platform for the mucin 16 overexpressing cells.

Keywords: Mesoporous silica nanoparticles; Mucin 16 aptamer; Ovarian cancer; Sunitinib; Targeted drug delivery.