期刊
NANO LETTERS
卷 16, 期 2, 页码 1118-1126出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.5b04343
关键词
Drug delivery; stimuli-responsive; tumor microenvironment; apoptosis; antiangiogenesis
类别
资金
- NC TraCS, NIH's Clinical and Translational Science Awards (CTSA, NIH grant) at UNC-CH [1UL1TR001111]
- State of North Carolina
- National Science Foundation (NSF)
Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a transformable core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.
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