Rapid Fc-mediated surface modification of liposomes with antibodies for selective targeting of pancreatic tumors.

Abstract

This study introduces a versatile platform for targeted drug delivery that addresses the complexities of conventional immunoliposome preparation. Traditional methods for conjugating a monoclonal antibody (mAb) to the surface of liposomes require target-specific chemical modification for each antibody, frequently resulting in suboptimal ligand orientation, steric hindrance of the antigen-binding sites, and a profound lack of modularity across different targeting systems. We developed Universal Particles (UPs), which are liposomal nanocarriers displaying high-affinity secondary antibodies on their surface. This design enables rapid, non-covalent functionalization by instantly binding to the constant (Fc) region of any whole-molecule primary targeting antibody without the need for chemical modification, thereby promoting a highly accessible, outward-facing display of the antigen-binding domains. In vitro experiments confirmed that UPs successfully functionalized with primary antibodies, leading to specific molecular recognition and enhancing cellular uptake of anti-Muc1/Muc4 UPs by Panc02 pancreatic cancer cells. Analytical flow cytometry confirmed the high expression of these target antigens in the Panc02 line, with 99.5% of cells expressing Muc1 and 99.9% expressing Muc4. In vivo biodistribution studies validated the platform's versatility: αCD31 UPs showed increased accumulation in the lungs, while dual anti-Muc1/Muc4 UPs demonstrated significantly enhanced tumor accumulation in a murine pancreatic tumor model compared with untargeted controls. The UP platform offers a simple approach for antibody-based liposomal targeting, providing a foundation for targeted delivery systems aimed at enhancing therapeutic selectivity and reducing off-target effects in preclinical models.