Conquering dual challenges: A sialic-modified liposome for targeting activated neutrophils to tackle comorbid lung inflammation and cancer metastasis

Abstract

In clinical settings, cancer frequently coexists with multi-system diseases. Owing to compromised immune systems, patients with cancer exhibit an increased susceptibility to infections and inflammation. Notably, lung inflammation occurs with high incidence among these patients. Furthermore, the inflammatory milieu within the lungs often accelerates the metastasis of cancer, thereby enhancing mortality rates and posing substantial challenges for clinical management. To date, effective strategies addressing both lung inflammation and cancer concurrently are lacking. In this context, we introduce a novel therapeutic approach involving a sialic acid-lipid derivative (SA-PG10-C18) modified doxorubicin-curcumin co-loaded liposome (DOX/CUR-SAL). This formulation effectively targeted activated neutrophils, which are abundantly present in inflammatory and metastatic lung tissues. DOX/CUR-SAL notably inhibited neutrophil-mediated pro-inflammatory and pro-metastatic processes. Utilizing a newly established mouse model of acute lung injury (ALI) and metastasis comorbidity, DOX/CUR-SAL modulated the lung immune microenvironment and arrested the progression of both inflammation and metastasis, without inducing side effects. The treated animals demonstrated favorable survival conditions, persisting beyond 45 days. This innovative therapeutic strategy offers a novel concept and reference for treating comorbid conditions of tumors and inflammation, thus breaking the clinical impasse where lung inflammation and cancer metastasis have been treated separately.