1 Center for Research and Education in Nanobioengineering, University of South Florida College of Medicine, Tampa, FL, USA.
2 Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
Cell Transplant. 2017 Oct;26(10):1694-1702. doi: 10.1177/0963689717721223.
The toxic side effects of doxorubicin (Dox) limit its long-term use as a lung cancer chemotherapeutic. Additionally, drug delivery to the deep lung is challenging. To address these challenges, isolated rat Sertoli cells (SCs) were preloaded with Dox conjugated to lipid micelle nanoparticles (SC-DLMNs) and delivered to mouse lungs. These immunocompetent cells, when injected intravenously, travel to the lung, deliver the payload, and get cleared by the system quickly without causing any adverse reaction. We observed that SC-DLMNs effectively treated Lewis lung carcinoma 1-induced lung tumors in mice and the drug efficacy was comparable to SC-Dox treatment. Mice treated with SC-DLMNs also showed significantly less toxicity compared to those treated with SC-Dox. The encapsulation of Dox in lipid micelle nanoparticles reduced the toxicity of Dox and the SC-based delivery method ensured drug delivery to the deep lung without evoking any immune response. Taken together, these results provide a novel SC-based nanoparticle drug delivery method for improved therapeutic outcome of cardiotoxic antilung cancer drugs.
多柔比星(阿霉素)的毒副作用限制了其作为肺癌化疗药物的长期使用。此外,药物输送到肺部深处也具有挑战性。为了解决这些挑战,将阿霉素偶联到脂质体纳米颗粒(SC-DLMNs)中的分离大鼠支持细胞(SCs)进行预加载,并递送到小鼠肺部。当这些免疫活性细胞经静脉注射时,它们会转移到肺部,传递有效载荷,并迅速被系统清除,而不会引起任何不良反应。我们观察到,SC-DLMNs 可有效治疗小鼠的 Lewis 肺癌 1 诱导的肺肿瘤,并且药物疗效与 SC-Dox 治疗相当。与 SC-Dox 治疗的小鼠相比,用 SC-DLMNs 治疗的小鼠的毒性也明显降低。脂质体纳米颗粒包封阿霉素可降低阿霉素的毒性,而基于 SC 的递药方法可确保药物输送到肺部深处,而不会引起任何免疫反应。总之,这些结果为改善心脏毒性抗肺癌药物的治疗效果提供了一种新型基于 SC 的纳米药物递送方法。