title: Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer.
abstract: Docetaxel (DOC) is widely used as radiosensitizer in various tumors, including gastric cancer (GC), but its therapeutic effect remains to be improved. In this study, using docetaxel-loaded nanoparticles (DOC-NPs) based on gelatinase-stimuli strategy, we compared their radioenhancement efficacy with docetaxel in GC. Compared with DOC, radiosensitization of DOC-NPs was improved significantly (sensitization enhancement ratio increased 1.09-fold to 1.24-fold, P<0.01) in all three gelatinase overexpressing GC cells, while increased slightly (1.02-fold, P=0.38) in gelatinase deficient normal gastric mucosa cells. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), more effective DSBs and promoted apoptosis. More importantly, the radiosensitization efficacy of DOC-NPs (estimated as ''very active'') was more prominent than DOC (estimated as ''moderately active'') by intravenous injection in xenograft. In conclusion, DOC-NPs are highly selective radiosensitizers in gelatinase over-expressing tumors, and more effective than DOC. By manipulating the common microenvironment difference between tumor and normal tissue, gelatinase-mediated nanoscale delivery system serves as a potential strategy possessing both universality and selectivity for radiosensitizers.
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Fang-Bo
authors: FB
authors: Cui
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Ru-Tian
authors: RT
authors: Li
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Qin
authors: Q
authors: Liu
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Pu-Yuan
authors: PY
authors: Wu
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Wen-Jing
authors: WJ
authors: Hu
authors: Nanjing Medical University, Hanzhong Road 140, Nanjing 21008, PR China.
authors: Guo-Feng
authors: GF
authors: Yue
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Hui
authors: H
authors: Ding
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Li-Xia
authors: LX
authors: Yu
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China.
authors: Xiao-Ping
authors: XP
authors: Qian
authors: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 21008, PR China. Electronic address: baoruiliu@nju.edu.cn.
authors: Bao-Rui
authors: BR
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015153:Blotting, Western; D000077143:Docetaxel; D018093:Gelatinases; D006801:Humans; D051379:Mice; D058726:Nanoconjugates / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy; D011091:Polyesters; D011092:Polyethylene Glycols; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D043823:Taxoids / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D011091:Polyesters; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; C016240:polycaprolactone; D011092:Polyethylene Glycols; D018093:Gelatinases
keywords: Docetaxel; Gastric cancer; Gelatinase-stimuli strategy; Nanoparticles; Radiosensitizer