期刊
SCIENCE ADVANCES
卷 6, 期 4, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz1722
关键词
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资金
- Center of Innovation program from the Japan Science and Technology Agency
- Basic Science and Platform Technology Program for Innovative Biological Medicine from the Japan Agency for Medical Research and Development (AMED) [JP18am0301008]
- Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED [JP18cm0106202]
- Translational Research program: Strategic Promotion for practical application of Innovative medical Technology (TR-SPRINT) [JP19lm0203023]
- JSPS KAKENHI [18K18383, 18H04163, 15H04635]
- Five-star Alliance from the Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [15H04635, 18H04163, 18K18383] Funding Source: KAKEN
In the current clinical boron neutron capture therapy (BNCT), p-boronophenylalanine (BPA) has been the most powerful drug owing to its ability to accumulate selectively within cancers through cancer-related amino acid transporters including LAT1. However, the therapeutic success of BPA has been sometimes compromised by its unfavorable efflux from cytosol due to their antiport mechanism. Here, we report that poly(vinyl alcohol) (PVA) can form complexes with BPA through reversible boronate esters in aqueous solution, and the complex termed PVA-BPA can be internalized into cancer cells through LAT1-mediated endocytosis, thereby enhancing cellular uptake and slowing the untoward efflux. In in vivo study, compared with clinically used fructose-BPA complexes, PVA-BPA exhibited efficient tumor accumulation and prolonged tumor retention with quick clearance from bloodstream and normal organs. Ultimately, PVA-BPA showed critically enhanced antitumor activity in BNCT. The facile technique proposed in this study offers an approach for drug delivery focusing on drug metabolism.
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