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

Abstract

Dan Wang,1,2,* Xuefen Li,3,* Xinfang Li,4,* Anfeng Kang,4 Linhong Sun,4 Miao Sun,4 Feng Yang,4 Congjian Xu1 1Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People&amp;rsquo;s Republic of China; 2Department of Gynaecology and Obstetrics, Changzheng Hospital, Second Military Medical University, Shanghai, People&amp;rsquo;s Republic of China; 3Department of Nephrology, Jiulongpo People&amp;rsquo;s Hospital, Chongqing, People&amp;rsquo;s Republic of China; 4Inorganic Chemistry Department, School of Pharmacy, Second Military Medical University, Shanghai, People&amp;rsquo;s Republic of China*These authors contributed equally to this workCorrespondence: Feng YangInorganic Chemistry Department, School of Pharmacy, Second Military Medical University, Shanghai 200433, People&amp;rsquo;s Republic of ChinaTel +86 21 8187 1218Email [email protected] XuDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, People&amp;rsquo;s Republic of ChinaTel +86 21 33189900Email [email protected]: 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 &amp;mu;g/mL, much smaller than that of free DOX (363.2 &amp;mu;g/mL). The nanocomposites could effectively reverse resistance and induce apoptosis of MCF-7/ADR cells. The blood biochemistry parameters and H&amp;amp;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