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Cancer Lett. 2014 Apr 28;346(1):53-62. doi: 10.1016/j.canlet.2013.12.002. Epub 2013 Dec 11.

Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer.

Author information

1
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.
2
Nanjing Medical University, Hanzhong Road 140, Nanjing 21008, PR China.
3
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.

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.

KEYWORDS:

Docetaxel; Gastric cancer; Gelatinase-stimuli strategy; Nanoparticles; Radiosensitizer

PMID:
24333735
DOI:
10.1016/j.canlet.2013.12.002
[Indexed for MEDLINE]

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