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Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment

Authors Pan C, Liu Y, Zhou M, Wang W, Shi M, Xing M, Liao W

Received 27 July 2017

Accepted for publication 31 October 2017

Published 27 February 2018 Volume 2018:13 Pages 1119—1137


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster

Changqie Pan,1–3,* Yuqing Liu,2,3,* Minyu Zhou,1 Wensheng Wang,4 Min Shi,1 Malcolm Xing,2,3,5 Wangjun Liao1

1Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Department of Mechanical Engineering, 3Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; 4The Imaging Center, 999 Brain Hospital, Guangzhou, China; 5Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada

*These authors contributed equally to this work

Abstract: A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [[email protected]]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical (1H nuclear magnetic resonance) and physical (morphology and supermagnetic) characterization, [email protected] were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that [email protected] had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles ([email protected]), and caused cellular apoptosis. The [email protected] cellular uptake and intracellular internalization were clarified by fluorescence microscopy. [email protected] plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

Keywords: theranostics, magnetic nanoparticle, pH sensitivity, folate receptor targeting, breast cancer

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