Enhanced Cytotoxicity of Niosomal Copper Schiff-Base Complexes in MCF-7 Cells: Substituent Effects and Delivery Efficiency

Hosniyeh Forouzani; Ehsan Zare Mehrjardi; Hadi Kargar; Houriyeh Forouzani; Mahmood Dehghani Ashkezari

doi:10.31557/APJCB.2026.11.3.729

Authors

Hosniyeh Forouzani Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran. Medical Biotechnology Research Center, Ashk.C., Islamic Azad University, Ashkezar, Iran.
Ehsan Zare Mehrjardi Department of Industrial Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Hadi Kargar Department of Chemical Engineering, Faculty of Engineering, Ardakan University, Ardakan, Iran.
Houriyeh Forouzani Department of Biology, Yazd University, Yazd, Iran.
Mahmood Dehghani Ashkezari Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran. Medical Biotechnology Research Center, Ashk.C., Islamic Azad University, Ashkezar, Iran.

DOI:

https://doi.org/10.31557/APJCB.2026.11.3.729

Keywords:

cancer therapy, Breast cancer, Schiff-base complexes, Drug delivery, Cytotoxicity

Abstract

Introduction: Breast cancer is currently the leading cause of cancer-related mortality among women worldwide. If urgent actions are not taken, the number of women diagnosed with breast cancer globally is projected to nearly double. Treating cancer cells is a complex process due to the presence of diverse biological pathways. Therefore, the simultaneous delivery of multiple drugs can exert a synergistic effect on the treatment process. Additionally, nanocarriers must exhibit high biocompatibility with healthy cells. Advancements in nanocarrier-mediated drug delivery offer promising strategies for improving anticancer agent efficacy.

Objective: This study synthesized two novel copper Schiff-base complexes N, N’-bis (3-ethoxysalicylidene)-2,2-dimethyl-1,3-propanediamine Cu (II) (CuL^3OEt) and N, N’-bis (5-bromosalicylidene)-2,2-dimethyl-1,3-propanediamine Cu (II) (CuL^5Br) and compared their cytotoxicity against MCF-7 breast cancer cells in free and niosome-encapsulated forms.

Materials and Methods: Niosomes were prepared via the thin-film hydration method to enhance delivery efficiency. Characterization using Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) revealed uniform nanoparticles (87.8–243.3 nm).

Results: Cytotoxicity, assessed via MTT assay, showed niosome-encapsulated forms significantly reduced IC₅₀ values (e.g., CuL^3OEt: 8.24 μg/mL vs. 80.65 μg/mL free form at 72 hr, p < 0.05), indicating improved potency. Substituent effects (ethoxy vs. bromo) influenced outcomes, linked to hydrophobicity differences (logS -4.788 vs. -5.75). Given the higher molecular weight of CuL^5Br (530 g/mol) compared CuL^3OEt (460 g/mol), the loading efficiency was 13.26% and 90.43%, respectively.

Conclusion: These findings highlight niosomal delivery’s potential to enhance Cu Schiff-base complex efficacy, laying a foundation for further preclinical studies.