期刊
ADVANCED FUNCTIONAL MATERIALS
卷 24, 期 16, 页码 2295-2304出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201303222
关键词
drug delivery; combination cancer therapy; site-specific delivery; nanomedicine; apoptosis
类别
资金
- Joint Biomedical Engineering Department at NCSU and UNC-CH
- NC State Faculty Research and Professional Development Award
- State of North Carolina and the National Science Foundation (NSF)
- China Scholarship Council
A programmed drug-delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core-shell-based nanodepot consisting of a liposomal core and a crosslinked-gel shell (designated Gelipo) is developed for the sequential and site-specific delivery (SSSD) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin (Dox). As a small-molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half-maximal inhibitory concentration (IC50) of TRAIL and Dox co-loaded Gelipo (TRAIL/Dox-Gelipo) toward human breast cancer (MDA-MB-231) cells is 83 ng mL(-1) (Dox concentration), which presents a 5.9-fold increase in the cytotoxicity compared to 569 ng mL(-1) of Dox-loaded Gelipo (Dox-Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA-MB-231 xenograft tumor animal model.
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