Sertoli Cells Loaded with Doxorubicin in Lipid Micelles Reduced Tumor Burden and Dox-Induced Toxicity

Abstract

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.