Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 8, Issue 27, Pages 17016-17022Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b04580
Keywords
self-assembly; polymer; peptide; temperature-responsive; cancer
Funding
- National Basic Research Program of China (973 Program) [2013CB932701]
- National Natural Science Foundation of China [21374026, 51473188, 21304023, 51303036, 51573032]
- Program of Beijing Municipal Science and Technology [Z141100000214008]
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We herein report a thermocontrolled strategy for realizing in situ conformational transition of polymer peptide conjugates at cell surfaces to manipulate and monitor HER2 receptor clustering, which finally result in effective breast cancer cell proliferation inhibition. Functional paring motifs (HBP) are covalently linked to a synthetic thermoresponsive polymer PNIPAAm to incorporate temperature control properties to HER2 targeting peptide. At 40 degrees C, the PNIPAAm polymers collapse and act as a shield to block the aggregation of HBP. Upon cooling to 35 degrees C, polymers are in their extended state and HBP are expose in aqueous and aggregate subsequently with enhanced fluorescence, allowing for promoting and in situ monitoring of receptor clustering. Ultimately, HER2 receptor clustering leads to cytoplasmic domain phosphorylation, which further results in effective cancer cell proliferation inhibition. We envision that this useful approach has the potential to be applied for molecule-targeted tumor therapy.
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