title: Cisplatin-loaded polymeric nanoparticles: characterization and potential exploitation for the treatment of non-small cell lung carcinoma.
abstract: 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)nGlu] 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 (5mg/kg cisplatin eq.) showed much longer survival rates (median survival time: 51days) as compared with mice treated with free cisplatin (median survival time: 18days), 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.
authors.affiliation: College of Pharmacy, Jilin University, Changchun 130021, Jilin, PR China; The People's Liberation Army 208th Hospital 461 Clinical Departments, Changchun 130021, Jilin, PR China.
authors.forename: Chunshan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Jilin University, Changchun 130021, Jilin, PR China. Electronic address: sundejun@163.com.
authors.forename: Dejun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: ztang@ciac.ac.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: The People's Liberation Army 208th Hospital 461 Clinical Departments, Changchun 130021, Jilin, PR China.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002850:Chromatography, Gel; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003848:Deoxyguanine Nucleotides / Q000737:chemistry; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011817:Rabbits; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016019:Survival Analysis
chemical_list: D003848:Deoxyguanine Nucleotides; D012996:Solutions; C579712:methoxypoly(ethylene glycol)-block-poly(glutamic acid); D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; C007257:2'-deoxyguanosine 5'-phosphate; D002945:Cisplatin
keywords: Cisplatin; Glutamic acid; Metabolism; NSCLC; Nanoparticle