Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, China.
Int J Pharm. 2022 Jun 10;621:121805. doi: 10.1016/j.ijpharm.2022.121805. Epub 2022 May 6.
As a first-line anticancer drug, sunitinib (SUN) can significantly inhibit tumor growth through an antiangiogenic effect. The nanocarrier drug-delivery strategy has been rapidly developed to improve therapeutic efficiency and drug safety. This study designed an intelligent liposome-like nanoporphyrin to broaden the application range of sunitinib. Additionally, we suggest that this personalized drug decoration and loading design can achieve more different functions. In this study, lipid-purpurin18 conjugates (Pp18-lipids) were synthesized by conjugating photosensitizer purpurin-18 (Pp18) with a phospholipid. Then, a porphyrin nano-delivery system (iPlipo-SUN) was developed by iRGD-modified Pp18-lipids-embedded liposome-carrying SUN. The system confers the targeted light-triggered SUN release, phototoxic properties, and antiangiogenesis onto iPlipo-SUN to multi-directionally suppress tumor growth. IPlipo-SUN was more effective than a maximum-tolerated dose of free SUN with its spatiotemporal control of drug release and intrinsic therapeutic effects. Therefore, the iPlipo-SUN offers new prospects for synergistic treatment that can be extended to explore tumor regrowth inhibition in clinical application.
舒尼替尼（Sunitinib）作为一种一线抗癌药物，通过抗血管生成作用能显著抑制肿瘤生长。纳米载体药物递送策略已迅速发展，以提高治疗效率和药物安全性。本研究设计了一种智能类脂质体卟啉纳米载体，以拓宽舒尼替尼的应用范围。此外，我们建议这种个性化药物修饰和加载设计可以实现更多不同的功能。在本研究中，通过将光敏剂卟啉-18（Pp18）与磷脂偶联，合成了脂质-卟啉 18 缀合物（Pp18-lipids）。然后，通过 iRGD 修饰的嵌入载有舒尼替尼的脂质体的 Pp18-lipids 制备了卟啉纳米递药系统（iPlipo-SUN）。该系统赋予 iPlipo-SUN 靶向光触发的 SUN 释放、光毒性和抗血管生成作用，从而多方位抑制肿瘤生长。iPlipo-SUN 的效果优于最大耐受剂量的游离舒尼替尼，其具有药物释放的时空控制和内在治疗作用。因此，iPlipo-SUN 为协同治疗提供了新的前景，可以扩展到临床应用中探索肿瘤复发抑制。
