Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release.

Abstract

Herein, a new nanodrug of azobenzene-functionalized interfacial cross-linked reverse micelles (AICRM) with 5-fluorouracil loading (5-FU@AICRM) is reported. Upon irradiation with 530 nm light in water, the surface azobenzenes of the nanoparticles change from polar cis-conformation to nonpolar trans-conformation, resulting in the aggregation of 5-FU@AICRM within minutes. Simultaneously, the conformation change unlocks hydrophilic 5-FU with a strong water immigration propensity, allowing them to spray out from the AICRM quickly. This fast release ensures a thorough release of the drug, before the aggregates are internalized by adjacent cells, making it possible to achieve deep tissue penetration. A study of in vivo anticancer activity in A549 tumor-bearing nude mice shows that the tumor inhibition rate (TIR) of 5-FU@AICRM is up to ≈86.2%, 31.6% higher than that of group without green light irradiation and 20.7% higher than that of carmofur (CF, a hydrophobic analog of 5-FU)-loaded AICRM (CF@AICRM), in which CF is released slowly under light irradiation because of its hydrophobicity. Fast drug release upon nanodrug aggregation provides a good solution for balancing the contradiction of "aggregation and penetration" in tumor treatment with nanodrugs.

• Authors: Yongchao Yao, Xin Dai, Yifeng Tan, Ying Chen, Chunyan Liao, Tian Yang, Yun Chen, Yunlong Yu, Shiyong Zhang
• Journal: Advanced healthcare materials (Adv Healthc Mater) Vol. 10 Issue 3 Pg. e2001430 (02 2021) ISSN: 2192-2659 [Electronic] Germany
• PMID: 33274859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley-VCH GmbH.

Chemical References

• Micelles
• Fluorouracil

Topics

• Animals
• Cell Line, Tumor
• Drug Liberation
• Fluorouracil
• Mice
• Mice, Nude
• Micelles
• Nanoparticles
• Neoplasms