Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 27, Issue 46, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201703674
Keywords
cancer theranostics; local-regional therapy; prodrug vesicles; reactive oxygen species; triple-negative breast cancer
Categories
Funding
- National Basic Research Program of China [2013CB932704]
- National Natural Science Foundation of China [31671024, 31622025, 81521005]
- Youth Innovation Promotion Association CAS [2014218]
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A reactive oxygen species (ROS)-activatable doxorubicin (Dox) prodrug vesicle (RADV) is presented for image-guided ultrafast drug release and local-regional therapy of the metastatic triple-negative breast cancer (TNBC). RADV is prepared by integrating a ROS-activatable Dox prodrug, a poly(ethylene glycol) (PEG)-modified photosensitizer pyropheophorbide-a, an unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine, and cholesterol into one single nanoplatform. RADV is of extremely high drug loading ratio (27.5 wt%) by self-assembly of the phospholipid-mimic Dox prodrug into the liposomal bilayer membrane. RADV displays good colloidal stability to prevent premature drug leakage during the blood circulation and inert photochemotoxicity to avoid nonspecific side effect. RADV passively accumulates at tumor site through the enhanced permeability and retention effect when administrated systemically. Once deposited at the tumor site, RADV generates fluorescent and photoacoustic signals to guide near-infrared (NIR) laser irradiation, which can induce localized ROS generation, not only to trigger prodrug activation and ultrafast drug release but also conduct photodynamic therapy in a spatiotemporally controlled manner. In combination with NIR laser irradiation, RADV efficiently inhibits the tumor growth and distant metastasis of TNBC. Local-regional tumor therapy using intelligent theranostic nanomedicine might provide an alternative option for highly efficient treatment of the metastatic TNBC.
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