Nanotherapeutic macrophage-based immunotherapy for the peritoneal carcinomatosis of lung cancer

Abstract

Lung cancer is the top cause of cancer mortality in the world. Distant metastasis leads to high mortality. Abdominal metastasis of lung cancer is characterized by very poor prognosis and the median survival time is usually less than two months. Therefore, it is of clinical significance to develop a new effective method for the treatment of abdominal metastasis of lung cancer. Cell therapy has promoted the development of new technology and strategy in oncology. Macrophages, as an important component of solid tumors, have also attracted great attention as a promising strategy of cell therapy in oncology. However, the reinfusion of autologous macrophages would be easily “re-educated” by the tumor microenvironment into a phenotype that promotes tumor development. This work developed a potential therapy using celastrol nanoparticle-containing M1-like macrophages (NP@M1) as a combinatory therapeutic system. M1-like macrophages (M1Φ) not only can serve as a drug delivery carrier for celastrol but also as a biotherapeutic agent. In turn, the celastrol nanoparticles (NPs) can maintain an anticancer polarized status of M1Φ, and subsequently, the exocytosed NPs can also execute the tumor cell-killing effect. Such a system thus provides a “two-birds-one-stone” therapeutic strategy and a proof of concept for the currently incurable abdominal metastasis of lung cancer.