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

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.