期刊
ACTA BIOMATERIALIA
卷 18, 期 -, 页码 68-76出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.02.009
关键词
NSCLC; Glutamic acid; Cisplatin; Nanoparticle; Metabolism
资金
- National Natural Science Foundation of China [51173184, 51373168, 51473029, 51233004, 51390484]
- Ministry of Science and Technology of China [2011DFR51090]
- Program of Scientific Development of Jilin Province [20130206066GX, 20130727050YY, 20130521011JH]
Cisplatin-loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol 5K) nanoparticles (CDDP-NPs) were characterized and exploited for the treatment of non-small cell lung carcinoma (NSCLC). In vitro metabolism experiments showed that a glutamic acid 5-mPEG ester [CH3O(CH2CH2O)(n)Glu] was generated when the poly(L-glutamic acid)-g-methoxy poly(ethylene glycol 5K) (PLG-g-mPEG5K) was incubated with HeLa cells. This suggests that the poly(glutamic acid) backbone of the PLG-g-mPEG5K is biodegradable. Furthermore, the size of the CDDP-NPs in an aqueous solution was affected by varying the pH (5.0-8.0) and their degradation rate was dependent on temperature. The CDDP-NPs could also bind to the model nucleotide 2'-deoxyguanosine 5'-monophosphate, indicating a biological activity similar to cisplatin. The CDDP-NPs showed a significantly lower peak renal platinum concentration after a single systemic administration when compared to free cisplatin. In vivo experiments with a Lewis lung carcinoma (LLC) model showed that the CDDP-NPs suppressed the growth of tumors. In addition, LLC tumor-bearing mice treated with the CDDP-NPs (5 mg/kg cisplatin eq.) showed much longer survival rates (median survival time: 51 days) as compared with mice treated with free cisplatin (median survival time: 18 days), due to the acceptable antitumor efficacy and low systemic toxicity of CDDP-NPs. These results suggest that the CDDP-NPs may be successfully applied to the treatment of NSCLC. (C) 2015 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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