Quantifying Carcinoembryonic Antigen-like Cell Adhesion Molecule-Targeted Liposome Delivery Using Imaging Flow Cytometry

Carcinoembryonic antigen-like cell adhesion molecules (CEACAMs) are human cell-surface proteins that can exhibit increased expression on tumor cells and are thus a potential target for novel tumor-seeking therapeutic delivery methods. We hypothesize that engineered nanoparticles containing a known interaction partner of CEACAM, Neisseria gonorrhoeae outer membrane protein Opa, can be used to deliver cargo to specific cellular targets. In this study, the cell association and uptake of protein-free liposomes and Opa proteoliposomes into CEACAM-expressing cells were measured using imaging flow cytometry. A size-dependent internalization of liposomes into HeLa cells was observed through endocytic pathways. Opa-dependent, CEACAM1-mediated uptake of liposomes into HeLa cells was observed, with limited colocalization with endosomal and lysosomal trafficking compartments. Given the overexpression of CEACAM1 on several distinct cancers and interest in using CEACAM1 as a component in treatment strategies, these results support further pursuit of investigating Opa-dependent specificity and the internalization mechanism for therapeutic delivery.