期刊
THERANOSTICS
卷 5, 期 8, 页码 890-904出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.11821
关键词
polypeptide nanocarriers; site-specific releasing; combination cancer therapy; dual-pH response; drug resistance
资金
- National Natural Science Foundation of China [21304099, 51203162, 51103159, 51373177, 31470961]
- National High Technology Research and Development Program [2014AA020708, 2012AA022703, 2012AA020804]
- Instrument Developing Project of the Chinese Academy of Sciences [YZ201253, YZ201313]
- Open Funding Project of the National Key Laboratory of Biochemical Engineering [Y22504A169]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA09030301-3]
- Hebei Province Hundred Talents Program [BR2-202]
- Three Three Three Talents Project of Hebei Province [A201401002]
- Key Basic Research Special Foundation of Science Technology Ministry of Hebei Province [14961302D]
- Training Program for Innovative Research Team and Leading Talent in Hebei Province University [LJRC024]
To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.
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