title: Radiosensitization of TPGS-emulsified docetaxel-loaded poly(lactic-co-glycolic acid) nanoparticles in CNE-1 and A549 cells.
abstract: Docetaxel is among the most effective radiosensitizers. It is widely used as radiosensitizer in many tumors, including head and neck carcinoma. Nevertheless, poor solubility and severe hypersensitivity limit its clinical use and its therapeutic effect remains to be improved. In this study, docetaxel-loaded polymeric nanoparticles were prepared by nanoprecipitation method to be new radiosensitizer with lower side effects and higher efficacy. The physiochemical characteristics of the nanoparticles were studied. Two human tumor cell lines which are resistant to radiotherapy were used in this research. We have compared the radioenhancement efficacy of docetaxel-loaded nanoparticles with docetaxel in A549 and CNE-1 cells. Compared with docetaxel, radiosensitization of docetaxel-loaded nanoparticles was improved significantly (sensitization enhancement ratio in A549 increased 1.24-fold to 1.68-fold when the radiation was applied 2 h after the drug, p < 0.01, sensitization enhancement ratio in CNE-1 increased 1.32-fold to 1.61-fold, p < 0.05). We explored the mechanisms for the radiosensitization efficiency and the difference between docetaxel and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, promoted apoptosis and the role of D-alpha-tocopheryl polyethylene glycol 1000 succinate which will enhance the cell uptake and inhibit the multiple drug resistance. Moreover, the radiosensitization efficacy of docetaxel-loaded nanoparticles was more prominent than docetaxel. In conclusion, tocopheryl polyethylene glycol 1000 succinate-emulsified docetaxel-loaded PLGA nanoparticles were more efficacious and fewer adverse effects were observed than with the commercial docetaxel formulation. Thus, PLGA nanoparticles hold promise as a radiosensitizing agent.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Wuhan, PR China Sun Yat-Sen University Cancer Center, Guangdong, China State Key Laboratory of Oncology in South China, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Wuhan, PR China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chu
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Qingle
authors.initials: Q
authors.lastname: Song
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Wuhan, PR China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Mu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Wuhan, PR China.
authors.forename: Shuangbing
authors.initials: S
authors.lastname: Xu
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, PR China National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Wuhan, PR China yangkunyu@medmail.com.cn.
authors.forename: Kunyu
authors.initials: K
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Drug-radiation interaction; cancer predisposition; cell cycle; nanoparticles; radiosensitivity