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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Dual agent loaded PLGA nanoparticles enhanced antitumor activity in a multidrug-resistant breast tumor eenograft
Yan Chen1, Xue-Lian Zheng2, Dai-Long Fang3
1State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. yanzai1112@sina.com.
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.
Insights
This study developed PLGA nanoparticles with vincristine and verapamil to treat multidrug-resistant breast cancer. The novel formulation demonstrated reduced toxicity and superior efficacy in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug-resistant breast cancer presents significant therapeutic challenges.
- Limited efficacy and high toxicity of current treatments necessitate novel approaches.
Purpose of the Study:
- To develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles for synergistic co-delivery of vincristine (VCR) and verapamil (VRP).
- To evaluate the efficacy and toxicity of this formulation against multidrug-resistant breast cancer models.
Main Methods:
- Formulation of PLGA nanoparticles (PLGANPs) co-encapsulating VCR and VRP at a 1:250 molar ratio.
- Assessment of drug synergism, nanoparticle stability (lyophilization), in vitro drug release, and acute toxicity.
- Evaluation of in vivo anti-tumor efficacy using MCF-7/ADR human breast tumor xenografts.
Main Results:
- A VCR/VRP molar ratio of 1:250 exhibited significant synergism in multidrug-resistant MCF-7/ADR cells.
- Lyophilized PLGANPs maintained desirable characteristics and synergistic drug release.
- Co-encapsulated nanoparticles showed reduced acute toxicity compared to free drug combinations.
- The nanoparticle formulation achieved the most effective inhibition of tumor growth in vivo.
Conclusions:
- PLGA nanoparticles offer a promising platform for co-delivering chemotherapeutics and chemosensitizers.
- This strategy holds potential for improving the clinical treatment of multidrug-resistant breast cancer.
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