Fenretinide (4-HPR), a synthetic retinoid, has shown its antitumor activity in many tumor types with low cytotoxicity to normal cells and high clinical safety. However, the low water solubility limits its further biological applications. To increase solubility, 4-HPR was conjugated with methoxy polyethylene glycol carboxylic acid (mPEG_2K-COOH) by an ester linkage between the phenol hydroxyl of 4-HPR and the carboxyl of mPEG_2K-COOH. The 4-HPR-PEG_2K conjugate micelles had mean size of 76.70 ± 1.248 nm with a narrow distribution and a low critical micelle concentration. In vitro cytotoxicity studies showed the micelles have higher cytotoxicity to A2780s and MCF-7 cells. Its IC₅₀ was 4.7 and 4.1-fold lower than the free 4-HPR, respectively. Importantly, in vivo pharmacokinetic studies, the AUC of 4-HPR was found to be 2.3-fold higher in 4-HPR-PEG_2K micelles compared to free 4-HPR. And the 4-HPR-PEG_2K micelles had higher antitumor activity. Meanwhile, the histopathology analysis exhibited that the micellar treatment decreased the viability of A2780s cells and increased the level of induced apoptosis. Therefore, the enhanced activity of 4-HPR by the method of conjugation with mPEG_2K-COOH could hopefully provide new insights into the matter of ovarian cancer and breast cancer treatment.

Fenretinide（4-HPR）是一种合成类维生素A，已显示出对多种肿瘤的抗肿瘤活性，对正常细胞的细胞毒性低，临床安全性高。但是，低水溶性限制了其进一步的生物学应用。为了增加溶解度，通过4-HPR的酚羟基与mPEG _2K -COOH的羧基之间的酯键将4-HPR与甲氧基聚乙二醇羧酸（mPEG _2K -COOH）缀合。4-HPR-PEG _2K共轭胶束的平均粒径为76.70±1.248 nm，分布窄，临界胶束浓度低。体外细胞毒性研究表明，胶束对A2780s和MCF-7细胞具有更高的细胞毒性。其IC ₅₀分别比游离的4-HPR低4.7和4.1倍。重要的是，在体内药代动力学研究中，发现4-HPR-PEG _2K胶束的4-HPR的AUC比游离4-HPR高2.3倍。而4-HPR-PEG _2K胶束具有较高的抗肿瘤活性。同时，组织病理学分析表明，胶束处理降低了A2780s细胞的活力并增加了诱导凋亡的水平。因此，通过与mPEG _2K -COOH结合的方法增强了4-HPR的活性，有望为卵巢癌和乳腺癌的治疗提供新的见解。