Magnetically Driven Photosensitive Nanorobots with Dual-Modal Imaging for Enhanced Photothermal-Photodynamic Cancer Therapy

Abstract

Conventional phototherapy for cancer faces significant challenges, including limited tissue penetration depth, poor tumor-targeting specificity, and suboptimal therapeutic efficacy, which hinder its clinical application. The development of intelligent nanorobotic systems that can be precisely controlled and monitored offers a promising avenue to overcome these limitations. In this study, we designed and fabricated a novel magnetically driven photosensitive nanorobot (MDPNR) for enhanced cancer therapy. The MDPNRs were constructed by integrating superparamagnetic iron oxide (Fe₃O₄) nanoparticles, plasmonic gold nanoparticles (AuNPs), and the photosensitizer Indocyanine Green (ICG) within a mesoporous silica nanoparticle (MSN) framework. This multifunctional design enables active tumor targeting under the guidance of an external magnetic field, combined with dual-modal imaging capabilities (fluorescence and photoacoustic imaging) for real-time therapeutic monitoring. Upon accumulation at the tumor site, the MDPNRs were activated by a single 808 nm near-infrared (NIR) laser, triggering simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT). The synergistic action of localized hyperthermia and reactive oxygen species (ROS) generation was investigated for its enhanced tumor-killing effect. The synthesized MDPNRs showed a saturation magnetization of 45.8 emu/g (enabling magnetic response velocity up to 125.5 ), a high photothermal conversion efficiency of 52.3%, and 15-fold higher ROS generation efficiency compared to free ICG under 808 nm NIR irradiation (1.5 W/cm²). In a 4T₁ breast cancer mouse model, the MDPNRs demonstrated remarkable tumor accumulation (>85% enrichment at the tumor site) under magnetic guidance. The dual-modal imaging provided clear visualization of the nanorobots’ biodistribution and therapeutic response. The combined PTT-PDT treatment resulted in significant tumor growth inhibition (>90%) and prolonged survival with negligible systemic toxicity. This work presents a sophisticated and precisely controllable nanorobotic platform that integrates active targeting, dual-modal imaging, and synergistic phototherapy. The MDPNRs offer a powerful strategy to enhance the precision and efficacy of cancer treatment, providing a solid foundation for future clinical translation.