Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 18, Pages 5057-5061Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201801641
Keywords
betaines; net charge; pH-responsiveness; polymers; targeted delivery
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Funding
- Basic Science and Platform Technology Program for Innovative Biological Medicine from Japan Agency for Medical Research and Development [JP17am0301008]
- Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED [JP17cm0106202]
- Center of Innovation (COI) program from Japan Science and Technology Agency (JST)
- Five-star Alliance from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- JSPS KAKENHI from JSPS [17H04743, 17K19481, 15H04635, 16K15104]
- Grants-in-Aid for Scientific Research [17K19481, 16K15104, 16F16407, 17H04743, 16F16058, 15H04635] Funding Source: KAKEN
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Polyzwitterions are employed as coating polymers for biomaterials to induce an antifouling property on the surface. Fine-tuning the betaine structure switches the antifouling property to be interactive with anionic tissue constituents in response to a tumorous pH gradient. The ethylenediamine moiety in the carboxybetaine enabled stepwise protonation and initiated the di-protonation process around tumorous pH (6.5). The net charge of the developed polyzwitterion (PGlu(DET-Car)) was thus neutral at pH7.4 for antifouling, but was cationic at pH6.5 for interaction with anionic constituents. Quantum dots coated with PGlu(DET-Car) exhibited comparable stealth and enhanced tumor accumulation relative to the PEG system. The present study provides a novel design of smart switchable polyzwitterion based on a precise control of the net charge.
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