Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, PR China.
Colloids Surf B Biointerfaces. 2022 Aug;216:112515. doi: 10.1016/j.colsurfb.2022.112515. Epub 2022 Apr 22.
Wogonin (Wog) plays an important role in human diseases, especially cancer and inflammatory diseases, but its poor solubility, unstable metabolism and low bioavailability greatly limit its application in biomedical fields. Therefore, we developed a temperature-dependent method to encapsulate wogonin into a novel ferritin-based nanocarrier. To improve the loading capacity and stability, the human H chain ferritin (HFtn) was functionalized with a repetitive polypeptide sequence composed of proline (Pro), alanine (Ala), and serine (Ser) in different residues lengths (PAS10 and PAS30). Wogonin loading and release studies demonstrated that the encapsulation efficiency and stability of the PASylated nanocarriers were significantly higher than those of the wild type. PAS-HFtn-Wog exhibited enhanced cytotoxicity to MCF-7 breast cancer cells and HepG2 liver cancer cells. Notably, the PASylated HFtn, especially PAS30-HFtn greatly prolonged the pharmacokinetics of wogonin in the mice bloodstream. Therefore, wogonin-loaded PAS-HFtn may be a promising drug candidate for cancer therapy.
汉黄芩素（Wog）在人类疾病中起着重要作用，特别是癌症和炎症性疾病，但它的溶解度差、代谢不稳定和生物利用度低，极大地限制了它在生物医学领域的应用。因此，我们开发了一种温度依赖性方法，将汉黄芩素包封到一种新型的基于铁蛋白的纳米载体中。为了提高载药量和稳定性，用人 H 链铁蛋白（HFtn）与由脯氨酸（Pro）、丙氨酸（Ala）和丝氨酸（Ser）组成的重复多肽序列（PAS10 和 PAS30）进行功能化。汉黄芩素的负载和释放研究表明，PAS 化纳米载体的包封效率和稳定性明显高于野生型。PAS-HFtn-Wog 对 MCF-7 乳腺癌细胞和 HepG2 肝癌细胞表现出增强的细胞毒性。值得注意的是，PAS 化的 HFtn，特别是 PAS30-HFtn，极大地延长了汉黄芩素在小鼠血液中的药代动力学。因此，负载汉黄芩素的 PAS-HFtn 可能是癌症治疗的一种有前途的药物候选物。
