Tumor-targeted delivery of honokiol via polysialic acid modified zein nanoparticles prevents breast cancer progression and metastasis

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.