期刊
NANOSCALE
卷 8, 期 1, 页码 283-291出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5nr06734k
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资金
- National Natural Science Foundation of China [21174126, 51303154, 51573160, 21574114]
- Key Science Technology Innovation Team of Zhejiang Province [2013TD02]
- Research Fund for the Doctoral Program of Higher Education of China [20130101120177]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [[2015]311]
A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and click reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.
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