Magnetically actuated superparamagnetic liposomes for accurate photothermal therapy and <i>in situ</i> antitumor immunoactivation

Liposomes are widely employed in drug delivery due to their biocompatibility and biodegradability. However, their therapeutic efficacy remains constrained by passive diffusion and limited targeting specificity. Although ligand modification has the potential to enhance the targeting ability of liposomes, a series of challenges, including complex synthesis, high costs, and potential immunogenicity, tend to hinder its broader clinical translation. Here, we present a simple yet effective strategy for tumor-targeted drug delivery and multimodal synergistic therapy by integrating magnetically actuated liposomal particles with an external magnetic field. The Lipo-ION system, which is formulated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within liposomes, can achieve targeted accumulation at tumor sites under the guidance of a magnetic field, significantly improving delivery efficiency. Moreover, SPIONs enable photothermal effects and reactive oxygen species (ROS) generation under near-infrared (NIR) irradiation, leading to tumor cell apoptosis and macrophage polarization toward the pro-inflammatory M1 phenotype. Such immune modulation effectively reshapes the tumor microenvironment, enhancing anti-tumor efficacy. By circumventing the complex liposomal modification steps and elaborate manufacturing processes, this approach achieves targeted accumulation and multimodal synergy, presenting a promising clinical strategy for precise, efficient, and low-toxicity anti-tumor therapy.