Aloss Kenan, Hamar Peter
Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.
Pharmaceutics. 2023 Mar 9;15(3):893. doi: 10.3390/pharmaceutics15030893.
Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in research due to its high efficacy despite dose-limiting toxicities. Several strategies have been exploited to enhance the efficacy and safety profile of DOX. Liposomes are the most established approach. Despite the improvement in safety properties of liposomal encapsulated DOX (in Doxil and Myocet), the efficacy is not superior to conventional DOX. Functionalized (targeted) liposomes present a more effective system to deliver DOX to the tumor. Moreover, encapsulation of DOX in pH-sensitive liposomes (PSLs) or thermo-sensitive liposomes (TSLs) combined with local heating has improved DOX accumulation in the tumor. Lyso-thermosensitive liposomal DOX (LTLD), MM-302, and C225-immunoliposomal(IL)-DOX have reached clinical trials. Further functionalized PEGylated liposomal DOX (PLD), TSLs, and PSLs have been developed and evaluated in preclinical models. Most of these formulations improved the anti-tumor activity compared to the currently available liposomal DOX. However, the fast clearance, the optimization of ligand density, stability, and release rate need more investigations. Therefore, we reviewed the latest approaches applied to deliver DOX more efficiently to the tumor, preserving the benefits obtained from FDA-approved liposomes.
阿霉素（DOX）是一种强效抗癌药物，尽管存在剂量限制性毒性，但因其高效性而在研究中备受关注。人们已经探索了多种策略来提高DOX的疗效和安全性。脂质体是最成熟的方法。尽管脂质体包裹的DOX（如多柔比星脂质体和麦罗塔）的安全性有所改善，但其疗效并不优于传统DOX。功能化（靶向）脂质体是一种更有效的将DOX递送至肿瘤的系统。此外，将DOX包裹在pH敏感脂质体（PSL）或热敏脂质体（TSL）中并结合局部加热，可提高DOX在肿瘤中的蓄积。溶酶体热敏脂质体DOX（LTLD）、MM - 302和C225免疫脂质体（IL）- DOX已进入临床试验。进一步开发了功能化聚乙二醇化脂质体DOX（PLD）、TSL和PSL，并在临床前模型中进行了评估。与目前可用的脂质体DOX相比，这些制剂大多提高了抗肿瘤活性。然而，快速清除、配体密度的优化、稳定性和释放速率仍需更多研究。因此，我们综述了为更有效地将DOX递送至肿瘤而应用的最新方法，同时保留了FDA批准的脂质体所带来的益处。
