Methoxypoly(ethylene glycol)-block-Poly(L-glutamic acid)-Loaded Cisplatin and a Combination With iRGD for the Treatment of Non-Small-Cell Lung Cancers

• Published in: Macromolecular bioscience 2012-11, Vol.12 (11), p.1514-1523
• Main Authors: Song, Wantong, Li, Mingqiang, Tang, Zhaohui, Li, Quanshun, Yang, Yan, Liu, Huaiyu, Duan, Taicheng, Hong, Hua, Chen, Xuesi
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Applied sciences; Biological and medical sciences; block copolymers; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; cisplatin; Cisplatin - chemistry; Cisplatin - pharmacokinetics; Cisplatin - pharmacology; Drug Carriers - chemical synthesis; drug delivery systems; Exact sciences and technology; Humans; Hydrogen-Ion Concentration; iRGD; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Medical sciences; Mice; Mice, Nude; Micelles; Microscopy, Electron, Transmission; Organic polymers; Peptides, Cyclic - chemistry; Pharmacology. Drug treatments; Physicochemistry of polymers; poly(L-glutamic acid); Polyethylene Glycols - chemical synthesis; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemical synthesis; Properties and characterization; Special properties (catalyst, reagent or carrier); Survival Rate; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201200145

CDDP is loaded into methoxypoly(ethylene glycol)‐block‐poly(L‐glutamic acid) (mPEG‐b‐PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP‐loaded micelles show sustained cisplatin release in PBS, dose‐ and time‐dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP‐loaded micelles show an evident anti‐tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP‐loaded micelles and co‐administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG‐b‐PLG‐loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC. Cisplatin (CDDP) is loaded into mPEG‐b‐PLG and a combination with cyclic iRGD (CRGDKGPDC) is applied for non‐small‐cell lung cancer therapy. In vivo results show that the toxicity of CDDP is significantly reduced by incorporating into PLG, and the anti‐tumor effect is clearly increased when iRGD is coadministrated.