Journal article
Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer
Nanomedicine, Vol.13(3), pp.1301-1307
04/2017
DOI: 10.1016/j.nano.2016.11.007
PMCID: PMC5392447
PMID: 27884641
Abstract
The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to formulate poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) NPs carrying both CPP and DTX. The dually loaded NPs display differences in drug release kinetics and in vitro cytotoxicity based on the structure of the chosen CPP. Furthermore, NPs containing both drugs showed a significant improvement in treatment efficacy versus the free drug combination in vivo.
Combinations of cisplatin and docetaxel are effective against many cancers. However, combination chemotherapy can lead to increases in toxicity and imprecise exposure of target cells to a specific drug ratio leading to treatment resistance. Co-encapsulation within nanoparticles has shown clinical success with other chemotherapies in overcoming these complications. Therefore, we developed co-formulations of cisplatin and docetaxel in PLGA–PEG nanoparticles using cisplatin prodrugs for efficient encapsulation. The combination nanoparticles show significant improvements in the therapeutic index versus the free drugs in vitro and against murine lung cancer models. Cisplatin prodrug structure also dictated therapeutic efficacy likely due to differences in co-formulation properties. [Display omitted]
Details
- Title: Subtitle
- Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer
- Creators
- Jing Tian - School of Biological and Environmental Engineering, Tianjin Vocational Institute, Tianjin, PR ChinaYuangzeng Min - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAZachary Rodgers - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAXiaomeng Wan - Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAHui Qiu - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAYu Mi - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAXi Tian - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAKyle T Wagner - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAJoseph M Caster - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAYanfei Qi - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAKyle Roche - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USATian Zhang - Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USAJianjun Cheng - Department of Materials Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL, USAAndrew Z Wang - Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Resource Type
- Journal article
- Publication Details
- Nanomedicine, Vol.13(3), pp.1301-1307
- DOI
- 10.1016/j.nano.2016.11.007
- PMID
- 27884641
- PMCID
- PMC5392447
- NLM abbreviation
- Nanomedicine
- ISSN
- 1549-9634
- eISSN
- 1549-9642
- Publisher
- Elsevier Inc
- Grant note
- 15JCYBJC21100 / Natural Science Foundation of Tianjin U54CA198999 / National Institutes of Health/National Cancer Institute R21 CA182322 / NIH/NCI R01CA178748-01 / National Institutes of Health/National Cancer Institute NIH-1T32CA196589 / Carolina Cancer Nanotechnology T32 Training Program 20110511 / Science & Technology Development Fund of Tianjin Education Commission for Higher Education
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047880902771
Metrics
17 Record Views