Synthesis and Characterization of Zinc-Loaded Mesoporous Silica Nanoparticles for pH-Responsive Cancer Drug Delivery

Carla Caramella 1*

This study determines Zn-loaded mesoporous silica nanoparticles as a scalable, pH-responsive drug delivery system for cancer therapy.

Abstract

Background: Cancer remains a global health challenge, with the World Health Organization estimating a doubling of cases by 2030 compared to 2008. Traditional chemotherapy is non-selective, harming both cancerous and healthy cells, which leads to systemic side effects. Nanoparticles (NPs), particularly mesoporous silica nanoparticles (MSNPs), offer a promising solution by enabling targeted drug delivery, minimizing harm to healthy tissues. This study focused on developing a pH-responsive drug delivery system (DDS) using zinc-loaded MSNPs, aiming to improve treatment specificity by exploiting the acidic tumor microenvironment. Methods: MSNPs were synthesized using a sol-gel process and loaded with zinc (Zn) using two methods: (i) calcination with zinc nitrate hexahydrate (ZnNt) at varying temperatures, and (ii) direct incorporation of Zn precursors (ZnNt, zinc acetate dihydrate, and zinc methoxyethoxide) into the MSNPs. The nanoparticles were characterized using Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), Scanning Transmission Electron Microscopy-Energy Dispersive X-ray Spectroscopy (STEM-EDS), and Fourier Transform Infrared Spectroscopy (FTIR). Zinc release at pH 7.4 (bloodstream) and pH 4.5 (tumor environment) was measured through dissolution studies, with quantification via Inductively Coupled Plasma Mass Spectrometry (ICP-OES). Results: Higher calcination temperatures increased zinc release at pH 4.5 but decreased it at pH 7.4, indicating greater stability under physiological conditions. Direct synthesis using ZnNt resulted in the most uniform zinc incorporation, leading to stable nanoparticle structure and consistent zinc distribution. Zinc release was more pronounced in acidic environments, demonstrating the pH-responsive nature of the Zn-MSNPs. Conclusion: Zn-loaded MSNPs show significant potential as a targeted drug delivery system for cancer treatment. The findings suggest that higher calcination temperatures enhance stability, while direct synthesis with ZnNt achieves optimal zinc loading. Future research should explore the therapeutic efficacy of these nanoparticles in vivo, aiming to improve cancer treatment with minimal side effects.

Keywords: Zinc-loaded nanoparticles, Mesoporous silica, Targeted drug delivery, pH-responsive release, Cancer treatment

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