Guo Chunhua, Cheng Xiaowei, Yang Yuxing, Wang Lijuan, Wang Wenfang, Shao Liping
Department of Obstetrics and Gynecology, Changzhou Cancer Hospital, Changzhou Fourth People's Hospital, Changzhou, Jiangsu, China.
Department of Obstetrics and Gynecology, Changzhou Cancer Hospital, Changzhou Fourth People's Hospital, Changzhou, Jiangsu, China.
Bioorg Med Chem Lett. 2025 Aug 1;123:130215. doi: 10.1016/j.bmcl.2025.130215. Epub 2025 Apr 1.
Honokiol (HK) is a polyphenol isolated from the Magnolia genus, a component of traditional Chinese herbal medicine, which can effectively suppress the growth of various tumors, including ovarian cancer. However, its low water solubility and lack of tumor-targeting ability have greatly hindered the clinical application of HK. Herein, a glutathione (GSH)-sensitive HK polyprodrug was prepared using HK as the backbone. An EpCAM-specific aptamer and poly(ethylene glycol) (PEG) were then conjugated to the HK polyprodrug, and the resulting polyprodrug was assembled into nanoparticles (NPs) in water. The HK polyprodrug-formed NPs achieved high drug loading and GSH-responsive drug release. Moreover, after optimization, HK polyprodrug NPs (A/P-PHK NP40), formed by aptamer-modified and PEG-modified prodrug at a feed molar ratio of 2: 3, exhibited the highest ability to target EpCAM-overexpressing ovarian cancer cells. A/P-PHK NP40 also demonstrated a greater cell growth inhibition effect in ovarian cancer cells compared to free HK and control HK NPs. All in all, this work reported a novel strategy for HK delivery based on microenvironment responsiveness polyprodrug, which provided a potential method for ovarian cancer targeting therapy.
厚朴酚（HK）是从木兰属植物中分离出的一种多酚，是传统中药的一种成分，能够有效抑制包括卵巢癌在内的多种肿瘤的生长。然而，其低水溶性和缺乏肿瘤靶向能力极大地阻碍了HK的临床应用。在此，以HK为骨架制备了一种谷胱甘肽（GSH）敏感的HK多聚前药。然后将一种上皮细胞黏附分子（EpCAM）特异性适配体和聚乙二醇（PEG）与HK多聚前药偶联，并将所得多聚前药在水中组装成纳米颗粒（NPs）。由HK多聚前药形成的NPs实现了高载药量和GSH响应性药物释放。此外，经过优化，由适配体修饰和PEG修饰的前药以2:3的进料摩尔比形成的HK多聚前药纳米颗粒（A/P-PHK NP40）对过表达EpCAM的卵巢癌细胞表现出最高的靶向能力。与游离HK和对照HK纳米颗粒相比，A/P-PHK NP40在卵巢癌细胞中也表现出更大的细胞生长抑制作用。总而言之，这项工作报道了一种基于微环境响应性多聚前药的HK递送新策略，为卵巢癌靶向治疗提供了一种潜在方法。
