A Multifunctional Nanocarrier Platform Based on Zinc–Amine–Graphene Oxide Functionalized Mesoporous Silica for Targeted Breast Cancer Therapy

A Multifunctional Nanocarrier Platform Based on Zinc–Amine–Graphene Oxide Functionalized Mesoporous Silica for Targeted Breast Cancer Therapy
Niyayesh Akhtari,¹ Hassan Noorbazargan,^2,*
1. Department of Biology, Faculty of Sciences, Parand branch of Tehran Azad University, Tehran, Iran
2. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Introduction: Breast cancer continues to be one of the most significant causes of cancer-related deaths among women around the world, with triple-negative breast cancer (TNBC) being among the most challenging to treat, largely due to its aggressiveness and absence of targeted drugs. Although conventional chemotherapeutic treatment options do work, they usually lack selectivity, provide general toxicity throughout the body, and produce drug resistance. Nanocarrier drug delivery systems can provide efficient delivery vehicles to improve drug solubility, pharmacokinetics, as well as provide targeted delivery. Among the many studied nanocarrier drug delivery systems, mesoporous silica nanoparticles (MSNs) are of significant interest to scientists and researchers. The unique properties of mesoporous silica nano carriers, such as high surface area, tunable pore sizes, and the ability to functionalize MSNs with other reagents, make for attractive application options. We have created a new multifunctional nanocarrier called Zn-MSN-NH₂-GO for the selective delivery of doxorubicin (DX) to triple-negative breast cancer (TNBC) cells. The nanoformulations essentially benefit from the drug-loading potential of HSNs, the pH-sensitive coordination properties of Zn (zinc), the targeting and stabilizing properties of NH₂ groups (amine groups), as well as the improved biocompatible dispersibility properties of GO (graphene oxide).
Methods: In this process, MSNs were prepared by the templating agent of tetraethyl orthosilicate (TEOS) and cetyltrimethylammonium bromide (CTAB), followed by surface functionalization via amine groups with 3-aminopropyltriethoxysilane (APTES), and then the incorporation of Zn via coordination with the amino groups. Graphene oxide (GO) was prepared via a modified Hummers' method and was electrostatically assembled onto the surface of the nanoparticles to create the Zn-MSN-NH₂-GO nanocarrier. The nanocarrier was loaded with doxorubicin (DX) by incubating the nanoparticles in phosphate buffer and determining the drug loading efficiency using UV–Vis spectrophotometry. The release profile of DX was determined at pH 7.4 and 5.4 using delivery via a dialysis method. Physicochemical properties were determined using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and zeta potential determination. The in vitro cytotoxicity against MDA-MB-231 breast cancer cells and normal human fibroblasts was assessed using cytotoxicity via the MTT assay. A panel of apoptotic and metastatic markers (Bax, Bcl-2, Caspase-3, MMP-9) and miR-193 expression was assessed via qPCR to assess the therapeutic effect of the DX-loaded nanocarrier.
Results: Physicochemical characterization confirmed the spherical shape with a nanoscale size of Zn-MSN-NH2-GO particles, and the success of charge loading and stable entrapment of DX at physiological pH. The nanoformulations presented a pH-responsive drug release profile, with little release at physiological pH (7.4), and rapid release under acidic pH (5.4) conditions, the latter version mimicking the tumor microenvironment. This controlled release behavior promotes targeted delivery to cancer cells and will maximize drug accumulation while minimizing off-target effects. In vitro studies demonstrated that DX-loaded Zn-MSN-NH2-GO had greater cytotoxicity for triple-negative breast cancer cells (MDA-MB-231) than both free DX, while preserving greater biocompatibility with normal human fibroblasts. The nanoformulations upregulate pro-apoptotic markers, including Bax, Caspase-3, and miR-193, while downregulating anti-apoptotic and metastatic markers such as Bcl-2 and MMP-9.
Conclusion: Overall, the data demonstrate that MZNG is a potential new targeted drug delivery system with superior therapeutic efficacy in the treatment of breast cancer. Further in vivo studies are needed to demonstrate the clinical relevance of this platform.
Keywords: Cancer Nanomedicine; Mesoporous Silica Nanoparticles; Doxorubicin; Controlled release; Breast Cancer