4.8 Article

Supramolecular Radiosensitizer Based on Hypoxia-Responsive Macrocycle

期刊

ADVANCED SCIENCE
卷 9, 期 6, 页码 -

出版社

WILEY
DOI: 10.1002/advs.202104349

关键词

calixarene; drug delivery; radiotherapy; supramolecular chemistry; tumor hypoxia

资金

  1. National Natural Science Foundation of China [52073306, 81971731, U20A20259, 31961143004]
  2. NCC Fund [NCC2020FH04]
  3. Young Elite Scientists Sponsorship Program by Tianjin [TJSQNTJ-2020-18]
  4. National Science Fund for Distinguished Young Scholars of Tianjin [18JCJQJC47300]
  5. Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019-RC-HL-014, 2018PT35031]
  6. CAMS Innovation Fund for Medical Sciences [2021-I2M-042]

向作者/读者索取更多资源

This study reports an innovative supramolecular radiotherapy strategy that utilizes the complexation of a hypoxia-responsive macrocycle with a small-molecule radiosensitizer to achieve efficient tumor destruction. The strategy exhibits high tumor accumulation and efficient cellular internalization, and achieves a high sensitizer enhancement ratio value.
Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia-responsive macrocycle with small-molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host-guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A center dot AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation-mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent-based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

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