Magnetically driven bionic nanorobots enhance chemotherapeutic efficacy and the tumor immune response via precise targeting

Abstract

We developed magnetically driven bionic drug-loaded nanorobots (MDNs) to accurately target tumors and deliver chemotherapy agents using a customized three-dimensional (3D) magnetic manipulation platform (MMP) system to precisely control their movement mode. MDNs were based on polyethylene glycol-modified homogeneous ultrasmall iron oxide nanoparticles (7.02 ± 0.18 nm). Doxorubicin (12% ± 2% [w/w]) was encapsulated in MDNs by an imide bond. MDNs could imitate the movement mode of a school of wild herrings (e.g., re-dispersion/arrangement/vortex/directional movement) to adapt to the changing and complex physiological environment through the 3D MMP system. MDNs overcame blood flow resistance and biological barriers using optimized magnetic driving properties according to <i>in vivo</i> imaging (magnetic resonance imaging and fluorescence) and histopathology. The performance of fabricated MDNs was verified through cells and tumor-bearing mouse models. The MDNs showed high efficiency of drug delivery and targeting at the tumor site (>10-fold), lower toxicity than free doxorubicin (5 mg/kg body weight), activated immune response in the tumor site, and significantly lengthened survival for mice. The synergistic interaction between MDNs and the 3D MMP system underscores the immense potential of this drug delivery system, indicating a potential revolution in the field of tumor chemotherapy.