Department of Biomedical Engineering , University at Buffalo, State University of New York , Buffalo , New York 14260 , United States.
Mol Pharm. 2018 Sep 4;15(9):3682-3689. doi: 10.1021/acs.molpharmaceut.8b00052. Epub 2018 Apr 2.
Chemophototherapy (CPT) is an emerging tumor treatment that combines phototherapy and chemotherapy. Long-circulating (LC) liposomes can stably incorporate 2 mol % porphyrin-phospholipid (PoP) in the bilayer and load doxorubicin (Dox) to generate LC-Dox-PoP liposomes, for single-agent CPT. Following intravenous administration to mice, LC-Dox-PoP liposomes (2 mg/kg Dox) circulated with similar blood concentration ranges produced by a typical human clinical dose of DOXIL (50 mg/m Dox). This dosing approach aims to achieve physiologically relevant Dox and PoP concentrations as well as CPT vascular responses in mice bearing subcutaneous human pancreatic MIA PaCa-2 xenografts. Phototreatment with 2 mg/kg LC-Dox-PoP induced vascular permeabilization, leading to a 12.5-fold increase in Dox tumor influx estimated by a pharmacokinetic model, based on experimental data. Shorter drug-light intervals (0.5-3 h) led to greater tumoral drug deposition and improved treatment outcomes, compared to longer drug-light intervals. At 2 mg/kg Dox, CPT with LC-Dox-PoP liposomes induced tumor regression and growth inhibition, whereas chemotherapy using several other formulations of Dox did not. LC-Dox-PoP liposomes were well tolerated at the 2 mg/kg dose.
化疗光动力疗法（CPT）是一种新兴的肿瘤治疗方法，结合了光疗和化疗。长循环（LC）脂质体可以在双层中稳定地掺入 2 mol%的卟啉磷脂（PoP）并负载阿霉素（Dox），以生成 LC-Dox-PoP 脂质体，用于单一药物 CPT。静脉注射到小鼠体内后，LC-Dox-PoP 脂质体（2 mg/kg Dox）的血液浓度范围与 DOXIL（50 mg/m Dox）的典型人类临床剂量相似。这种给药方法旨在在携带皮下人胰腺 MIA PaCa-2 异种移植物的小鼠中实现生理相关的 Dox 和 PoP 浓度以及 CPT 血管反应。用 2 mg/kg LC-Dox-PoP 进行光疗会引起血管通透性增加，根据基于实验数据的药代动力学模型，估计 Dox 肿瘤内流增加了 12.5 倍。与较长的药物光照间隔（0.5-3 h）相比，较短的药物光照间隔（0.5-3 h）会导致更多的肿瘤药物沉积并改善治疗效果。在 2 mg/kg Dox 时，LC-Dox-PoP 脂质体的 CPT 会引起肿瘤消退和生长抑制，而其他几种 Dox 制剂的化疗则没有。LC-Dox-PoP 脂质体在 2 mg/kg 剂量下耐受良好。
