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Cellular senescence is the results of aging and age-related diseases, and the development of anti-aging methods may improve health and extend longevity. The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo, but has poor water solubility and limited bioavailability. In this study, a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides (WPI-GOS) Maillard conjugate, which could recognize senescence associated β-galactosidase in senescent cells. The fisetin nanoparticles possessed a high encapsulation efficiency, excellent dispersibility in water, good storage stability and well biocompatibility. Moreover, they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy, and inhibit the oxidative stress-induced cellular senescence in vitro. Thus, this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.


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A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Show Author's information Shuai Houa,b,c,dChutong LaibYukun Songa,c,dHaitao Wanga,c,dJialu Nia,c,dMingqian Tana,c,d,( )
Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian 116044, China
National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China
Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China

Peer review under responsibility of Tsinghua University Press.

Highlights

1. A food-grade and senescent cell-targeted fisetin delivery system is developed.

2. The WPI-GOS Maillard conjugate-based nanoparticles can target senescent cells.

3. Fisetin-loaded targeted nanoparticles alleviate cellular senescence.

Abstract

Cellular senescence is the results of aging and age-related diseases, and the development of anti-aging methods may improve health and extend longevity. The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo, but has poor water solubility and limited bioavailability. In this study, a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides (WPI-GOS) Maillard conjugate, which could recognize senescence associated β-galactosidase in senescent cells. The fisetin nanoparticles possessed a high encapsulation efficiency, excellent dispersibility in water, good storage stability and well biocompatibility. Moreover, they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy, and inhibit the oxidative stress-induced cellular senescence in vitro. Thus, this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

Keywords: Nanoparticle, Targeted delivery, Fisetin, Cellular senescence

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Publication history

Received: 27 September 2022
Revised: 26 October 2022
Accepted: 18 November 2022
Published: 25 September 2023
Issue date: March 2024

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© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

Acknowledgements

Acknowledgements

This work was supported by Dalian Youth Science and Technology Star Project (2020RQ121), the National Science Fund for Distinguished Young Scholars of China (31925031), Doctoral Scientific Research Foundation of Liaoning Province (2020-BS-211), and Liaoning Province Education Administration (J2020101).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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