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Upon irradiation with 530\u00a0nm light in water, the surface azobenzenes of the nanoparticles change from polar <jats:italic>cis<\/jats:italic>\u2010conformation to nonpolar <jats:italic>trans<\/jats:italic>\u2010conformation, resulting in the aggregation of 5\u2010FU@AICRM within minutes. Simultaneously, the conformation change unlocks hydrophilic 5\u2010FU 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\u2010bearing nude mice shows that the tumor inhibition rate (TIR) of 5\u2010FU@AICRM is up to \u224886.2%, 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\u2010FU)\u2010loaded 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 \u201caggregation and penetration\u201d in tumor treatment with nanodrugs.<\/jats:p>","DOI":"10.1002\/adhm.202001430","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T05:29:55Z","timestamp":1607059795000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release"],"prefix":"10.1002","volume":"10","author":[{"given":"Yongchao","family":"Yao","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  29 Wangjiang Road Chengdu 610064 China"},{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu 610041 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