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Life sciences · Journal article
Frontiers in Pharmacology · October 20, 2026
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Introduction Psoralen (PSO) is an anticancer agent with a potential role in breast cancer management. Its clinical application, however, is significantly limited by poor aqueous solubility and low bioavailability. Therefore, the development of advanced PSO delivery systems is essential to enhance its therapeutic potential. Methods In this study, a novel nano-delivery platform was constructed by encapsulating PSO into zein nanoparticles (NPs) followed by surface modification with fucoidan (Fu), yielding PSO-Z/F NPs. Results Successful surface modification was confirmed by a reversal in ζ potential from positive values to −24.8 ± 0.02 mV, an increase in particle size to 129.23 ± 0.18 nm, characteristic changes in sulfate-related Fourier transform infrared spectroscopy (FTIR) bands, and the appearance of an S 2p signal in X-ray photoelectron spectroscopy (XPS). The PSO-Z/F NPs exhibited a uniform spherical morphology, with an encapsulation efficiency of 73.13 ± 0.98% and a drug-loading capacity of 5.40 ± 0.35%. Cellular uptake of PSO-Z/F NPs was 1.6-fold higher than that of uncoated PSO-Z NPs ( P < 0.05). In vitro, PSO-Z/F NPs significantly suppressed the proliferation, migration, and invasion of 4T1 breast cancer cells. Specifically, wound closure rate decreased from 29.13 ± 3.33 % in the control group to 5.02 ± 2.86% ( P < 0.001). Compared with the PSO group, the number of migrated cells decreased from 220 ± 33 to 146 ± 20 ( P < 0.01), while that of invaded cells decreased from 144 ± 21 to 90 ± 8 ( P < 0.05). Moreover, PSO-Z/F NPs increased the total apoptosis rate from 6.45% in the control group to 17.98% ( P < 0.01). In addition, hemolysis assays showed reduced hemolytic activity, while serum-incubation studies confirmed improved colloidal stability, as evidenced by minimal changes in particle size and PDI over 7 days. Notably, in vivo and ex vivo fluorescence analysis of tumors and major organs in 4T1 tumor-bearing mice showed efficient tumor accumulation of PSO-Z/F NPs, and pharmacodynamic studies indicated enhanced tumor growth inhibition with an acceptable biosafety profile. Discussion Overall, PSO-Z/F NPs may provide a potential nanoparticle-based delivery strategy for improving the therapeutic application of psoralen in breast cancer.