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

Authors Wang D, Li X, Li X, Kang A, Sun L, Sun M, Yang F, Xu C

Received 3 May 2019

Accepted for publication 2 September 2019

Published 18 September 2019 Volume 2019:14 Pages 7665—7679

DOI https://doi.org/10.2147/IJN.S214377

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 3

Editor who approved publication: Dr Mian Wang


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’s Republic of China; 2Department of Gynaecology and Obstetrics, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Nephrology, Jiulongpo People’s Hospital, Chongqing, People’s Republic of China; 4Inorganic Chemistry Department, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Feng Yang
Inorganic Chemistry Department, School of Pharmacy, Second Military Medical University, Shanghai 200433, People’s Republic of China
Tel +86 21 8187 1218
Email yangfeng1008@126.com
Congjian Xu
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, People’s Republic of China
Tel +86 21 33189900
Email xucongjian@fudan.edu.cn

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


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