Protocatechuic Acid-Based Supramolecular Hydrogel Targets SerpinB9 to Achieve Local Chemotherapy for OSCC.
Protocatechuic Acid-Based Supramolecular Hydrogel Targets SerpinB9 to Achieve Local Chemotherapy for OSCC.
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DOI：
10.1021/acsami.2c07534
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发表时间：
2022-07
影响因子：
9.5
通讯作者：
Zaiye Li;Lideng Cao;Chengcan Yang;Tiannan Liu;Hang Zhao;Xiao Luo;Qianmin Chen
中科院分区：
文献类型：
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作者：
Zaiye Li;Lideng Cao;Chengcan Yang;Tiannan Liu;Hang Zhao;Xiao Luo;Qianmin Chen
原儿茶酸（PCA）是一种存在于日常蔬菜和水果中的天然酚酸。值得注意的是，PCA被证明可以抑制SerpinB9 （Sb9）的生物学功能，并表现出良好的抗肿瘤作用，在癌症治疗中具有很大的潜力。然而，短的半衰期限制了PCA在癌症治疗中的广泛应用。为了克服PCA的不足，我们将PCA与另一种具有强自组装特性的天然产物异鸟苷（isoG）结合，开发出一种具有良好生物相容性和可注射性的多功能超分子水凝胶，显著延长了PCA的释放时间，并在体外和体内发挥了显著的抗癌作用。此外，我们令人惊讶地发现，PCA不仅可以靶向Sb9，还可以通过激活JNK/P38通路，降低ROS水平，修复癌症干细胞来抑制癌症的发展。总之，我们的研究结果表明，这种基于pca的水凝胶可以作为一种多功能的水凝胶系统，具有相当的抗癌作用，提供潜在的局部给药，结合靶向治疗和化疗，以一种简单的方式。
Protocatechuic acid (PCA) is a natural phenolic acid present in daily vegetables and fruits. Notably, PCA was demonstrated to inhibit the biological function of SerpinB9 (Sb9) and exhibit an excellent antitumor effect, showing great potential in cancer treatment. However, the short half-life time limits PCA's wide application against cancers. To overcome this shortage of PCA, we integrated PCA and another natural product with strong self-assembling properties, isoguanosine (isoG), to develop a novel multifunctional supramolecular hydrogel with good biocompatibility and injectability, which remarkably lengthens the releasing time of PCA and exerts considerable anticancer effects in vitro and in vivo. Besides, we surprisingly found that PCA could not only target Sb9 but also restrain cancer development through activating the JNK/P38 pathway, decreasing the ROS level, and repairing cancer stemness. In all, our results demonstrate that this PCA-based hydrogel could act as a multifunctional hydrogel system equipped with considerable anticancer effects, providing potential local administration integrating with targeted therapy and chemotherapy in one simple modality.