Iron Nanoparticles for Low-Power Local Magnetic Hyperthermia in Combination with Immune Checkpoint Blockade for Systemic Antitumor Therapy
Yu Chao, Guobin Chen, Chao Liang, Jun Xu, Ziliang Dong, Xiao Han, Chao Wang, and Zhuang Liu*
Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China
Magnetic hyperthermia (MHT) utilizing heat generated by magnetic nanoparticles under alternating magnetic field (AMF) is an effective local tumor ablation method but can hardly treat metastatic tumors. In this work, we discover that pure iron nanoparticles (FeNPs) with high magnetic saturation intensity after being modified by biocompatible polymers are stable in aqueous solution and could be employed as a super effective MHT agent to generate sufficient heating under a low power AFM. Effective MHT ablation of tumors is then achieved, using either locally injected FeNPs or intravenously injected FeNPs with the help of locally applied tumor-focused constant magnetic field to enhance the tumor accumulation of those nanoparticles. We further demonstrate that the combination of FeNP-based MHT with local injection of nano-adjuvant and systemic injection of anti-cytotoxic Tlymphocyte antigen-4 (anti-CTLA4) checkpoint blockade would result in systemic therapeutic responses to inhibit tumor metastasis. A robust immune memory effect to prevent tumor recurrence is also observed after the combined MHT-immunotherapy. This work not only highlights that FeNPs with appropriate surface modification could act as a super effective MHT agent but also presents the great promises of combining MHT with immunotherapy to achieve long-lasting systemic therapeutic outcome after local treatment.