Elongated Magnetic Nanorobots with Multi-Enzymatic Cascades for Active In Vivo Tumor Targeting and Enhanced Chemodynamic Therapy
Di Li, Chi Zhang, Qirong Xiong, Wylie Liu, Yingwei Tang, Li Liang, Kanyi Pu, Hongwei Duan
Abstract
Targeted delivery of therapeutic agents to malignant tissues is crucial for enhancing clinical outcomes and reducing side effects. Magnetic nanorobots (MNRs) present a promising strategy for controlled delivery, leveraging external magnetic fields to achieve precise in vivo targeting. This work develops elongated MNRs comprising linearly arranged magnetic nanoparticles linked by metal-polyphenol complexes (MPCs) for magnetic-field-directed active tumor targeting and synergistic tumor therapy. The MNRs are created by assembling 30 nm Fe 3 O 4 nanoparticles, tannic acid, and ferrous ions (Fe 2+ ) under a uniform magnetic field, resulting in elongated chain-like structures fixed by MPCs, which also promotes peroxidase-like activity. These structures show a greater magnetic response than individual nanoparticles, offering flexibility in magnetic manipulation. The MPCs coating allows tailored surface modifications with glucose oxidase, copper ions (Cu 2+ ), and human serum albumin (HSA), producing colloidally stable MNRs with a built-in multienzymatic cascade (MNRs@GOx/Cu/HSA) that consumes glucose, generates • OH, and depletes the antioxidant glutathione (GSH). Collectively, surface-engineered multifunctional MNRs demonstrate improved in vivo tumor targeting driven by external magnetic fields, leading to efficient localized chemodynamic therapy. The tailored structural and functional properties of the developed MNRs render them suitable for targeted cargo delivery, minimally invasive surgery, and localized treatments in disease sites.