title: Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer.
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.
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Yuangzeng
authors.initials: Y
authors.lastname: Min
authors.affiliation: 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.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Rodgers
authors.affiliation: 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.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Wan
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mi
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Kyle T
authors.initials: KT
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Caster
authors.affiliation: 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.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: 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.
authors.forename: Kyle
authors.initials: K
authors.lastname: Roche
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: 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: zawang@med.unc.edu.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004338:Drug Combinations; D011355:Prodrugs; D043823:Taxoids; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077143:Docetaxel; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: Cisplatin prodrugs; Combination therapy; Docetaxel; Drug delivery; PLGA–PEG