title: Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs.
abstract: Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs.
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences , Wuhan, 430071, P. R. China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, University of Chinese Academy of Sciences , Beijing, 100190, P. R. China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences , Wuhan, 430071, P. R. China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences , Wuhan, 430071, P. R. China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Hao
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences , Wuhan, 430071, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, University of Chinese Academy of Sciences , Beijing, 100190, P. R. China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Genetic Engineering, Biospectroscopy and Metabolomics, School of Life Sciences, Fudan University , Shanghai, 200433, P. R. China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences , Wuhan, 430071, P. R. China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310058, P. R. China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D016503:Drug Delivery Systems; D004734:Energy Metabolism / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D011091:Polyesters / Q000633:toxicity; D011092:Polyethylene Glycols / Q000633:toxicity
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D053769:Nanocapsules; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel
keywords: metabonomics; nanosafety; nanotoxicity; nuclear magnetic resonance (NMR); polymer nanoparticles