In this work, we developed
polysialic acid (PSA) modified
zein nanoparticles for targeted delivery of
honokiol (HNK) to enhance drug delivery efficiency and specific biodistribution at
tumor sites. The antisolvent precipitation and electrostatic interaction methods were employed to fabricate the PSA-
Zein-HNK nanoparticles, which exhibited mean size of 107.2 ± 10.1 nm and HNK encapsulation efficiency of 79.2 ± 2.3%. The PSA-
Zein-HNK maintained a uniform dispersion in serum for 48 h, implying the improved
colloid stability of
zein nanoparticles via PSA coating. The cellular uptake of PSA-Zein-Cou6 nanoparticles in 4 T1 cells was 2.58-fold higher than non-targeting Zein-Cou6. In addition, the IC50 value at 48 h for PSA-
Zein-HNK (4.37 μg/mL) was significantly higher than the
Zein-HNK (7.74 μg/mL). Enhanced
tumor accumulation of the PSA-
Zein-HNK was confirmed in 4 T1
breast cancer-bearing mice by near-infrared fluorescence imaging, resulting in desirable antitumor efficacy and favorable biosafety. Besides, compared with non-targeting
zein nanoparticles, the PSA-
Zein-HNK achieved a higher
tumor growth inhibition rate of 52.3%. In particular, the
metastasis of
breast cancer to the lung or liver was remarkably suppressed by PSA-
Zein-HNK. Together, our results demonstrated that the PSA-
Zein-HNK could be a potential
tumor-targeted drug delivery strategy for efficient treatment of
breast cancer.