The Development of Antibody-Functionalized Liposomes via Click Chemistry for Precision Targeting of PD-L1-Positive Ovarian Cancer

Cancer treatment faces significant difficulties with chemotherapy, often leading to severe side effects. This encourages the need for research on innovative, selective therapies for targeted drug delivery, particularly using nanotechnology-based liposomes as carriers. Liposomes, spherical nanocarriers, can encapsulate drugs and be functionalized for targeted delivery, boosting drug accumulation in cancer cells while minimizing harm to healthy tissues. However, to introduce the targeting ability, the attachment of biomarkers with liposomes always faces several challenges such as insufficient and unstable binding, improper functionalization, poor stability, and a tedious attachment process. This study developed an antibody-functionalized liposomal system, covalently conjugated with Atezolizumab, a monoclonal antibody against programmed death-ligand 1 (PD-L1) to form antibody-lipid-doxorubicin (Ab-Lip-Dox), a targeted nanocarrier system. Unlike conventional attachment methods, this study employs a covalent conjugation strategy based on click chemistry between a modified antibody and functionalized liposomes, representing the innovation of the work. It selectively delivered higher doxorubicin (Dox) to ovarian cancerous SKOV-3 cells overexpressing PD-L1. The nanocarrier, with an optimized size (100-200 nm) and a doxorubicin concentration (1 μg/mL), effectively reduces systemic toxicity and enhances drug accumulation in tumor cells through site-specific delivery. The success of this approach lays the groundwork for the development of next-generation targeted therapies for ovarian and other PD-L1-expressing cancers.