Intracellular delivery of anti-dengue envelope monoclonal antibodies via PEG-PLGA nanoparticles suppresses viral replication and attenuates hepatocyte apoptosis

Abstract

Dengue virus (DENV) infection remains a major global health threat, with no specific antiviral treatment currently approved. Monoclonal antibody (mAb) therapy represents a promising strategy for viral inhibition; however, conventional antibodies are largely restricted to extracellular compartments and lack access to intracellular viral replication sites. In this study, we encapsulated a cross-reactive mAb targeting the DENV envelope protein (m513) into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles to facilitate intracellular delivery. When applied to immortalized hepatocyte-like cells (imHCs), the formulation demonstrated efficient cellular uptake, low cytotoxicity, and significantly reduced intracellular viral RNA and protein levels. The resulting formulation consisted of mAb-loaded PEG-PLGA nanoparticles (∼100 nm in diameter) with spherical morphology and an encapsulation efficiency of approximately 50%. Furthermore, nanoparticle treatment significantly reduced hepatocyte apoptosis in infected cells. Collectively, these findings demonstrate that nanoparticle-mediated intracellular antibody delivery can overcome a key limitation of conventional antibody therapy and represents a mechanistically distinct antiviral strategy for DENV and other intracellular viral infections.