Photodynamic therapy - hypericin tetraether liposome conjugates and their antitumor and antiangiogenic activity
Photodynamic therapy - hypericin tetraether liposome conjugates and their antitumor and antiangiogenic activity
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DOI：
10.1080/10717544.2018.1531954
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发表时间：
2019-01-01
期刊：
影响因子：
6
通讯作者：
Bakowsky, Udo
中科院分区：
文献类型：
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作者：
Plenagl, Nikola;Duse, Lili;Bakowsky, Udo
光动力疗法（PDT）是一种成熟的非侵入性肿瘤治疗方法。疏水性天然色素金丝桃素在 PDT 中的应用显示出许多有吸引力的特性。因此，对生物系统或患者的给药需要在药物载体中进行配制，以实现足够的生物利用度。因此，通过薄膜水合方法将游离金丝桃素包封，或者通过脱水-再水化囊泡方法将金丝桃素-羟丙基-β-环糊精包合物（Hyp-HP beta CD）掺入常规或超稳定四醚脂质（TEL）脂质体中。所制备的纳米制剂的流体动力学直径范围在127至212 nm之间。这些结果由原子力显微镜证实。所有脂质体在生理条件下均表现出良好的稳定性。 TEL 脂质体倾向于构建更刚性的双层，比传统脂质体产生更高的封装效率。此外，血液相容性研究证实了静脉注射的适用性，溶血潜力低于 20%，凝血时间低于 50 秒。使用共聚焦显微镜证实了脂质体金丝桃素被人卵巢癌细胞 (SK-OV-3) 吸收，并通过途径研究进一步表征。结果表明，脂质组成和脂质体内金丝桃素定位影响绒毛尿囊膜（CAM）的抗血管作用。虽然金丝桃素 TEL 脂质体表现出对微血管系统的显着破坏，但环糊精中的药物 TEL 脂质体没有显示出任何效果。然而，两种制剂在治疗剂量范围内对 SK-OV-3 细胞产生严重的光细胞毒性。总之，金丝桃素 TEL 脂质体非常适合抗血管靶向，而 Hyp-HP beta CD TEL 脂质体可以以更受保护的方式将光敏剂递送到肿瘤部位。
Photodynamic therapy (PDT) is an established noninvasive tumor treatment. The hydrophobic natural occurring pigment hypericin shows a lot of attractive properties for the application in PDT. Hence, the administration to biological systems or patients requires the formulation in drug carriers enabling sufficient bioavailability. Therefore, free hypericin was encapsulated by the thin film hydration method or a hypericin-hydroxypropyl-beta-cyclodextrin inclusion complex (Hyp-HP beta CD) was incorporated by dehydration-rehydration vesicle method in either conventional or ultra-stable tetraether lipid (TEL) liposomes. The hydrodynamic diameter of the prepared nanoformulations ranged between 127 and 212 nm. These results were confirmed by atomic force microscopy. All liposomes showed a good stability under physiological conditions. TEL liposomes which tend to build more rigid bilayers, generate higher encapsulation efficiencies than their conventional counterparts. Furthermore, the suitability for intravenous application was confirmed by hemocompatibility studies resulting in a hemolytic potential less than 20% and a coagulation time less than 50 sec. The uptake of liposomal hypericin into human ovarian carcinoma cells (SK-OV-3) was confirmed using confocal microscopy and further characterized by pathway studies. It was demonstrated that the lipid composition and intraliposomal hypericin localization influenced the anti-vascular effect in the chorioallantoic membrane (CAM). While hypericin TEL liposomes exhibit substantial destruction of the microvasculature drug-in-cyclodextrin TEL liposomes showed no effect. Nevertheless, both formulations yielded severe photocytotoxicity in SK-OV-3 cells in a therapeutic dosage range. Conclusively, hypericin TEL liposomes would be perfectly suited for anti-vascular targeting while Hyp-HP beta CD TEL liposomes could deliver the photosensitizer to the tumor site in a more protected manner.