Microfluidic-assisted synthesis of integrin-targeting cRGD liposomes as a scalable strategy for theranostic applications in triple-negative breast cancer

Abstract

Triple negative breast cancer (TNBC) represents one of the most aggressive types of cancer, with a difficult treatment leading to poor prognosis of the disease. Herein we report the synthesis of a custom-made cyclic RGD peptide (cRGD), and its use in decorating liposomes for targeted drug delivery of doxorubicin to TNBC cells overexpressing integrin receptor αvβ3. Liposomes carrying dibenzocyclooctine groups on their surface were produced using an optimized large scale microfluidic-assisted approach and subsequently conjugated with cRGD bearing an acyl azide group by means of a click chemistry reaction. This functionalization promotes enhanced cellular uptake via integrin-mediated endocytosis. In vitro assessments confirm enhanced selectivity and cytotoxicity of cRGD-liposomes against triple-negative cancer cells, in addition to dual imaging capabilities by fluorescence and magnetic resonance techniques due to the incorporation of a fluorescent dye and gadolinium complex, respectively. These features support the potential of cRGD-liposomes as a promising platform for targeted drug delivery to specific cancer cell populations, establishing them as viable theranostic agents for precision medicine applications.