铁纳米颗粒用于低功率局部磁热疗联合免疫检查点阻断的系统抗肿瘤治疗。

Iron Nanoparticles for Low-Power Local Magnetic Hyperthermia in Combination with Immune Checkpoint Blockade for Systemic Antitumor Therapy.

机构信息

Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology , Soochow University , Suzhou , Jiangsu 215123 , China.

出版信息

Nano Lett. 2019 Jul 10;19(7):4287-4296. doi: 10.1021/acs.nanolett.9b00579. Epub 2019 Jun 5.

Abstract

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 supereffective 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 nanoadjuvant and systemic injection of anticytotoxic T-lymphocyte 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 supereffective MHT agent but also presents the great promises of combining MHT with immunotherapy to achieve long-lasting systemic therapeutic outcome after local treatment.

摘要

利用交变磁场(AMF)下磁性纳米粒子产生的热量的磁热疗(MHT)是一种有效的局部肿瘤消融方法,但很难治疗转移性肿瘤。在这项工作中,我们发现经过生物相容性聚合物修饰后的具有高饱和磁化强度的纯铁纳米粒子(FeNPs)在水溶液中稳定,可作为一种超强的 MHT 试剂,在低功率 AMF 下产生足够的加热。通过局部应用肿瘤聚焦恒磁场来增强这些纳米粒子在肿瘤中的积累,从而实现有效的 MHT 消融肿瘤。我们进一步证明,基于 FeNP 的 MHT 与局部注射纳米佐剂和全身注射抗细胞毒性 T 淋巴细胞抗原-4(抗 CTLA4)检查点抑制剂的联合应用,将导致全身性治疗反应,以抑制肿瘤转移。在联合 MHT-免疫治疗后,还观察到了强大的免疫记忆效应,以防止肿瘤复发。这项工作不仅强调了适当表面修饰的 FeNPs 可以作为一种超强的 MHT 试剂,而且还展示了将 MHT 与免疫疗法相结合,在局部治疗后实现持久的全身性治疗效果的巨大潜力。

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