Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 29, Issue 23, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201808462
Keywords
breast cancer; combinational therapy; irradiation responsiveness; retention effect; transformable nanomedicines
Categories
Funding
- National Natural Science Foundation of China [81872806, 31571016]
- Young Elite Scientists Sponsorship Program by CAST [2017QNR001]
- Sichuan Youth Science and Technology Innovation Research Team Funding [2016TD0001]
- Fundamental of Research Funds for the Central University [SCU2017A001]
- (State Key Laboratory of Polymer Physics and Chemistry in Changchun Institute of Applied Chemistry)
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Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe-Phe-Val-Leu-Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR-FFVLK-PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species-responsive paclitaxel dimer with thioketal linker (PTX2-TK), the resultant PTX2-TK@Ce6/BR-FFVLK-PEG nanomedicine serves as a potent chemo-photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX2-TK@Ce6/BR-FFVLK-PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg(-1) PTX and 3.3 mg kg(-1) Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.
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