Engineered Virus-Like Nanoparticles Enable Multimodal Protein Degradation for Enhanced Tumor Therapy.

Abstract

Virus-like particle (VLP) holds significant promise for drug delivery and cancer therapy; however, they encounter challenges related to structural stability and functional versatility. This study reports a biomimetic virus-like nanoparticle (VNP) platform, which is engineered through rational integration of lipid scaffolding, siRNA encapsulation, and surface-anchored DNA aptamer-based LYTAC (DbLYTAC). This modular design synergistically combines gene silencing with targeted protein degradation capabilities while enhancing structural stability. In vitro experiments validate the exceptional efficacy of the VNPs in achieving targeted protein degradation, while in vivo studies using animal models demonstrate their promising potential for tumor therapy. This approach establishes a paradigm-shifting platform that overcomes the limitations of protein-based viral mimics, paving the way for multifunctional nanotherapeutics in cancer therapy.