Dual Responsive Magnetic DCR3 Nanoparticles: A New Strategy for Efficiently Targeting Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer deaths globally. Unlike traditional molecularly targeted drugs, magnetically controlled drug delivery to micro/nanorobots enhances precision in targeting tumors, improving drug efficiency and minimizing side effects. This study develops a dual‐responsive, magnetically controlled drug delivery system using PEGylated paramagnetic nanoparticles conjugated with decoy receptor 3 (DCR3) antibodies. The clusters demonstrate capabilities for long‐range, magnetically driven control and molecular chemotaxis. Paramagnetic PEGylated particles form vortex‐ and liquid‐like drug moieties within a magnetically controlled system. Vortex‐like nanoparticle clusters exhibit high controllability and countercurrent movement, while liquid‐nanoparticle robot clusters display greater deformability. Upon loading with DCR3 antibodies, the particles navigate along DCR3‐protein gradients in blood and tissue, effectively targeting liver tumor sites in vivo. Clusters of DCR3‐coupled magnetic nanoparticles target cells that highly express DCR3, thereby effectively inhibiting tumor cell proliferation and migration. Compared with conventional nanomedicine, DCR3‐coupled magnetic nanoparticle clusters are capable of delivering controlled drugs over long distances and responding in a molecular‐targeting manner. This research is expected to significantly impact the field of precise tumor drug delivery.