Quercetin (Que) is a polyhydroxy flavonoid with strong inhibitory activity against cancer cells. However, the poor water solubility and low bioavailability of Que. limit its application in the functional food industry. In the present study, the nanoparticle loaded with Que. was prepared with whey isolate protein (WPI) stabilized by triphenylphosphonium bromide (TPP) and pectin (P) as wall materials. The formation mechanism, release of Que., and antitumor activity of nanoparticles were investigated. The results showed that the optimal ratio of WPI: TPP: Que.: P in the preparation of nanoparticles (WPI-TPP-Que-P) was 50:8:1:20 (w/w/w/w). The encapsulation rate of Que. in the WPI-TPP-Que-P was 82.64 % with a particle size of 261.7 nm and a zeta potential of -42.1 mV. Compared with WPI-TPP-Que, the retention rate of WPI-TPP-Que-P increased by 4.03 % after in vitro digestion. The release kinetic result indicated that WPI-TPP-Que-P release was dominated by non-Fickian diffusion. In addition, WPI-TPP-Que-P was taken in and achieved intracellular targeting to mitochondria and promoted apoptosis (apoptosis rate: 83.6 %) by decreasing mitochondrial membrane potential and IL-10 content and improving the content of TNF-α in HepG-2 cells. This study highlights the promising application of P-modified mitochondria-targeted nanocarriers for enhanced Que. delivery.

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http://dx.doi.org/10.1016/j.ijbiomac.2025.140383DOI Listing

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