2--deoxyguanosine-5--phosphate and Lung-Neoplasms

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.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Chromatography, Gel; Cisplatin; Deoxyguanine Nucleotides; Dynamic Light Scattering; Endocytosis; HeLa Cells; Hemolysis; Humans; Hydrodynamics; Hydrogen-Ion Concentration; Inhibitory Concentration 50; Kidney; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Particle Size; Polyethylene Glycols; Polyglutamic Acid; Rabbits; Solutions; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Survival Analysis