Sustained irrigation effect enhanced the accumulation and retention of ultra-long circulating nanoparticles in tumor

The development of ultra-long circulating nanodrug delivery systems have showed distinct advantage in maintaining the long-lasting tumor retention. Although the relationship between extended tumor retention and ultra-long plasma half-life was apparent, there was still a lack of experimental evidence to reveal the enhancement mechanism. Herein, we proposed a concept of Sustained Irrigation effect (SI effect) to elucidate that it was through sustained blood irrigation that the ultra-long circulating nanoparticles achieved long-lasting tumor retention. Besides, in order to intuitively verify the SI effect, we developed an ON-OFF-ON fluorescence switch technology. The ultra-long circulating delivery nanoparticle was constructed by encapsulating the protein with hydrophilic polymer shell. Nanoparticles with ultra-long plasma half-life (t(1/2)>40 h) fabricated by this method were employed as models for demonstrating the SI effect. The recovery of Cy5.5 fluorescence after the laser quenching meant the fresh Cy5.5-labeled nanoparticles were entering tumor, which confirmed the ultra-long circulating nanoparticles in blood could sustainedly irrigate to tumor. Our finding revealed the key mechanism by which ultra-long circulating NDDSs enhanced the tumor accumulation and retention, and provided experimental support for the development of ultra-long circulating delivery system in clinic. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

The development of ultra-long circulating nanodrug delivery systems has shown significant advantages in maintaining long-lasting tumor retention. This study proposes the concept of Sustained Irrigation effect (SI effect), which explains that the ultra-long circulating nanoparticles achieve prolonged tumor retention through sustained blood irrigation. An ON-OFF-ON fluorescence switch technology was developed to verify the SI effect. The findings reveal the key mechanism by which ultra-long circulating NDDSs enhance tumor accumulation and retention, providing experimental support for the development of ultra-long circulating delivery systems in clinical applications.