Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs

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• 作者：Yipeng Song ; Ruifang Zhao ; Yili Hu ; Fuhua Hao ; Ning Li ; Guangjun Nie ; Huiru Tang ; Yulan Wang
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：December 4, 2015
• 年：2015
• 卷：14
• 期：12
• 页码：5193-5201
• 全文大小：483K
• ISSN：1535-3907

文摘

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鈥揚LGA), 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鈥揚LGA, mPEG鈥揚LGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG鈥揚LGA 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鈥揚LGA 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鈥揚LGA packaging on the toxicity of the incorporated drugs.