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

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 approximate 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.

Automated summary

A new nanodrug system, AICRM loaded with 5-FU, is reported in this study. By activating the surface azobenzenes with light irradiation, rapid drug release is achieved, leading to enhanced anticancer activity and deep tissue penetration compared to traditional drug delivery systems.