Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Jing Tian; Yuangzeng Min; Zachary Rodgers; Xiaomeng Wan; Hui Qiu; Yu Mi; Xi Tian; Kyle T Wagner; Joseph M Caster; Yanfei Qi; Kyle Roche; Tian Zhang; Jianjun Cheng; Andrew Z Wang

doi:10.1016/j.nano.2016.11.007

Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Nanomedicine. 2017 Apr;13(3):1301-1307. doi: 10.1016/j.nano.2016.11.007. Epub 2016 Nov 21.

Authors

Jing Tian¹, Yuangzeng Min², Zachary Rodgers², Xiaomeng Wan³, Hui Qiu⁴, Yu Mi², Xi Tian², Kyle T Wagner², Joseph M Caster², Yanfei Qi⁵, Kyle Roche², Tian Zhang⁶, Jianjun Cheng⁷, Andrew Z Wang⁸

Affiliations

¹ School of Biological and Environmental Engineering, Tianjin Vocational Institute, Tianjin, PR China; 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; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² 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; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ 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; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁵ 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; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; School of Public Health, Jilin University, Changchun, Jilin, China.
⁶ Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
⁷ Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁸ 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; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: [email protected].

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.

Keywords: Cisplatin prodrugs; Combination therapy; Docetaxel; Drug delivery; PLGA–PEG.

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cell Line, Tumor
Cisplatin / administration & dosage*
Cisplatin / therapeutic use
Docetaxel
Drug Carriers / chemistry
Drug Combinations
Female
Humans
Lung / drug effects*
Lung / pathology
Lung Neoplasms / drug therapy*
Lung Neoplasms / pathology
Mice
Mice, Nude
Nanoparticles / chemistry*
Polyethylene Glycols / chemistry*
Polyglactin 910 / chemistry*
Prodrugs / administration & dosage
Prodrugs / therapeutic use
Taxoids / administration & dosage*
Taxoids / therapeutic use

Substances

Antineoplastic Agents
Drug Carriers
Drug Combinations
Prodrugs
Taxoids
poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
Docetaxel
Polyglactin 910
Polyethylene Glycols
Cisplatin

Abstract

MeSH terms

Substances

Grants and funding