Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles
Qin Liu1*, Ru-Tian Li1*, Han-Qing Qian2, Mi Yang1, Zhen-Shu Zhu2, Wei Wu2, Xiao-Ping Qian1, Li-Xia Yu1, Xi-Qun Jiang2, Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing 210008, China;...
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Dove Medical Press
2012
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oai:doaj.org-article:d8fb9aa097d64cf28643dfea3c0fabde2021-12-02T01:07:58ZGelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles1176-91141178-2013https://doaj.org/article/d8fb9aa097d64cf28643dfea3c0fabde2012-01-01T00:00:00Zhttp://www.dovepress.com/gelatinase-stimuli-strategy-enhances-the-tumor-delivery-and-therapeuti-a9108https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Qin Liu1*, Ru-Tian Li1*, Han-Qing Qian2, Mi Yang1, Zhen-Shu Zhu2, Wei Wu2, Xiao-Ping Qian1, Li-Xia Yu1, Xi-Qun Jiang2, Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing 210008, China; 2Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering College of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China*These authors contributed equally to this workAbstract: Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel “intelligent” nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere® (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.Keywords: drug delivery, stimuli-responsive, gelatinase, antitumor, docetaxelLiu QLi RTQian HQYang MZhu ZSWu WQian XPYu LXJiang XQLiu BRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 281-295 (2012) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Liu Q Li RT Qian HQ Yang M Zhu ZS Wu W Qian XP Yu LX Jiang XQ Liu BR Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| description |
Qin Liu1*, Ru-Tian Li1*, Han-Qing Qian2, Mi Yang1, Zhen-Shu Zhu2, Wei Wu2, Xiao-Ping Qian1, Li-Xia Yu1, Xi-Qun Jiang2, Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing 210008, China; 2Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering College of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China*These authors contributed equally to this workAbstract: Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel “intelligent” nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere® (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.Keywords: drug delivery, stimuli-responsive, gelatinase, antitumor, docetaxel |
| format |
article |
| author |
Liu Q Li RT Qian HQ Yang M Zhu ZS Wu W Qian XP Yu LX Jiang XQ Liu BR |
| author_facet |
Liu Q Li RT Qian HQ Yang M Zhu ZS Wu W Qian XP Yu LX Jiang XQ Liu BR |
| author_sort |
Liu Q |
| title |
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| title_short |
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| title_full |
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| title_fullStr |
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| title_full_unstemmed |
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| title_sort |
gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/d8fb9aa097d64cf28643dfea3c0fabde |
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