Lung cancer and microbiota

Lung cancer is a major health concern with limited effective treatments. Current therapies are typically administered intravenously and often lack specificity. Inhalation offers a promising alternative, as it may enhance therapeutic efficacy by reducing systemic exposure while increasing local bioavailability. Nanoparticles can be aerosolized and deposited at the air–blood barrier by inhalation. However, the lung microbiome may significantly influence the activity of anticancer drugs once they reach the lungs. Indeed, we observed that Streptococcus mitis and Prevotella bivia, lung microbiota strains, degrade clinically used anticancer drugs within few hours. Therefore, we synthesized two types of amphiphilic prodrugs: a PEGylated anticancer agent and an antimicrobial peptide (AMP) conjugated to anticancer drugs. Nanoprecipitation of these prodrugs yielded self-assembling nanocarriers that combined stealth characteristics with both anticancer and antimicrobial properties. Steady self-assemblies were obtained, containing either a single anticancer drug or a combination of two within the same object. The nanomedicines displayed hydrodynamic diameters ranging from 100 to 150 nm, with a polydispersity index < 0.2. Their critical aggregation concentrations were measured between 100 and 150 µM, and the assemblies exhibited a positive zeta potential due to the cationic charge of the AMP. Internalization into A549 lung cancer cells was confirmed by FACS analysis and confocal microscopy. Furthermore, the IC₅₀ values of the nanoobjects were determined in this cell line, ranging from 300 nM to 10 µM and demonstrating that the anticancer activity was preserved. In vivo evaluation of these nanomedicines is currently underway in an orthotopic lung cancer mouse model, with administration by nebulization, to assess the therapeutic potential of this approach. 

Conférence en anglais.