Magnetic And pH Dual-Responsive Nanoparticles For Synergistic Drug-Resistant Breast Cancer Chemo/Photodynamic Therapy

Abstract

Background

Drug resistance is one of the prime reasons of chemotherapy failure in breast cancer and is also an important factor affecting prognosis.

Purpose

In this study, we constructed a functional magnetic mesoporous silica-based nanocomposite (MMSN) for breast cancer chemotherapy/photodynamic therapy.

Methods

MMSN was characterized by scanning electron microscopy and transmission electron microscopy to observe the morphology. The size distribution and zeta potential of the MSNs were determined using Malvern Particle Size Analyzer. Anti-tumor activity in vitro was investigated by CCK-8 assay, flow cytometry and transwell experiment, and the anti-tumor activity in vivo was probed into by magnetic targeting, toxicity, and antitumor effects in breast cancer-bearing BABL/c nude mice.

Results

The results showed that the release of doxorubicin in the nanocomposites was pH sensitive, and the cumulative release rate reached 80.53% at 60 h under acidic conditions. The nanocomposites had a high cellular uptake ability in MCF-7/ADR cells, and the IC₅₀ value of the nanocomposites on MCF-7/ADR cells was 4.23 μg/mL, much smaller than that of free DOX (363.2 μg/mL). The nanocomposites could effectively reverse resistance and induce apoptosis of MCF-7/ADR cells. The blood biochemistry parameters and H&E staining results showed no serious adverse effects after treatment with the nanocomposites. Prussian blue staining showed that the nanocomposites were able to target tumor tissues in tumor-bearing mice under a magnetic field. The combined chemical/photodynamic therapy significantly inhibited tumor growth in vivo.

Conclusion

Nanocomposites with magnetic and pH dual-responsive performance has shown a promising platform for enhanced drug-resistant breast cancer treatment.

Keywords:

• magnetic mesoporous silica
• doxorubicin
• magnetic targeting
• pH responsive
• photodynamic therapy

Acknowledgments

This work was supported by a grant from National Key R&D Program of China (2016YFC1303100), the National Natural Science Foundation of China (21778022), Shanghai Natural Science Foundation (16ZR1444200), and National Science Foundation for Young Scientists of China (81603124).

Disclosure

The authors report no conflicts of interest in this work.