Next Article in Journal
Bacterial Cellular Engineering by Genome Editing and Gene Silencing
Next Article in Special Issue
Development of Lipid-Shell and Polymer Core Nanoparticles with Water-Soluble Salidroside for Anti-Cancer Therapy
Previous Article in Journal
ScChi, Encoding an Acidic Class III Chitinase of Sugarcane, Confers Positive Responses to Biotic and Abiotic Stresses in Sugarcane
Previous Article in Special Issue
Preparation and Characterization of Tripterygium wilfordii Multi-Glycoside Nanoparticle Using Supercritical Anti-Solvent Process
Int. J. Mol. Sci. 2014, 15(2), 2761-2772; doi:10.3390/ijms15022761
Article

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

1,†
, 2,†
, 1
, 1
, 1
, 1
, 1
, 1
, 3
 and 1,*
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 [331 KB, uploaded 19 June 2014]   |   Browse Figures

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.
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


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 Eenograft Model. Int. J. Mol. Sci. 2014, 15, 2761-2772.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert