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Correction published on 29 July 2016, see Int. J. Mol. Sci. 2016, 17(8), 1233.

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(2), 2761-2772; doi:10.3390/ijms15022761

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Xenograft Model

1
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
2
Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China
3
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Received: 30 December 2013 / Revised: 10 February 2014 / Accepted: 11 February 2014 / Published: 18 February 2014
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
View Full-Text   |   Download PDF [344 KB, 29 July 2016; original version 19 June 2014]   |  

Abstract

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. View Full-Text
Keywords: multidrug-resistant breast cancer; vincristine; verapamil; PLGA nanoparticles; co-encapsulation multidrug-resistant breast cancer; vincristine; verapamil; PLGA nanoparticles; co-encapsulation
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chen, Y.; Zheng, X.-L.; Fang, D.-L.; Yang, Y.; Zhang, J.-K.; Li, H.-L.; Xu, B.; Lei, Y.; Ren, K.; Song, X.-R. Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Xenograft Model. Int. J. Mol. Sci. 2014, 15, 2761-2772.

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