Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY.
Nektar Therapeutics, Formulations Group, San Francisco, CA.
Photochem Photobiol. 2023 Mar;99(2):844-849. doi: 10.1111/php.13677. Epub 2022 Aug 2.
Porphyrin-phospholipid (PoP) liposomes loaded with Doxorubicin (Dox) have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multidrug resistance (MDR) of cancer cells is a problematic phenomenon in which tumor cells develop resistance to chemotherapy. Herein, we report that Dox-resistant tumor cells can be ablated using our previously described formulation termed long-circulating Dox loaded in PoP liposomes (LC-Dox-PoP), which is a PEGylated formulation containing 2 mol. % of the PoP photosensitizer. In vitro studies using free Dox and LC-Dox-PoP showed that human ovarian carcinoma A2780 cells were more susceptible to Dox compared to the corresponding Dox-resistant A2780-R cells. When CPT was applied with LC-Dox-PoP liposomes, effective killing of both nonresistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC-Dox-PoP showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing subcutaneous Dox-resistant A2780-R tumor xenografts when they were irradiated with a red laser. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox-resistant tumors with CPT, suggesting that increased drug delivery was sufficient to induce ablation of resistant tumor cells.
载有阿霉素（Dox）的卟啉磷脂（PoP）脂质体已被证明是化学光疗（CPT）的有效载体。癌细胞的多药耐药（MDR）是一种有问题的现象，其中肿瘤细胞对化疗产生耐药性。在此，我们报告说，我们之前描述的一种制剂，即载有阿霉素的长循环 PoP 脂质体（LC-Dox-PoP），可以用于消融多药耐药的肿瘤细胞，该制剂是一种含有 2mol%的 PoP 光敏剂的聚乙二醇化制剂。使用游离 Dox 和 LC-Dox-PoP 的体外研究表明，与相应的多药耐药 A2780-R 细胞相比，人卵巢癌细胞 A2780 对 Dox 更敏感。当应用 CPT 时，观察到非耐药和耐药 A2780 细胞系均有效杀伤。一项体内研究评估 LC-Dox-PoP 的效率表明，当用红色激光照射携带皮下多药耐药 A2780-R 肿瘤异种移植物的无胸腺裸鼠时，有效缩小肿瘤并延长其存活时间。生物分布分析表明，CPT 可增强耐药肿瘤中的肿瘤药物摄取，表明增加药物递送足以诱导耐药肿瘤细胞消融。
