Tumor-associated macrophages (TAMs) play an important role in tumor development and progression. In particular, M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors. Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment. Iron oxide nanoparticles based magnetic hyperthermia therapy (MHT) is a classical approach to destroy tumor tissue with deep penetration depth. In this study, we developed a typical M2 macrophage-targeted peptide (M2pep) functionalized superparamagnetic iron oxide nanoparticle (SPIO) for magnetic resonance imaging (MRI)-guided MHT in an orthotopic breast cancer mouse model. The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability, high transverse relaxivity (149 mM⁻¹ s⁻¹) and satisfactory magnetic hyperthermia performance in vitro. In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT. The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor. In addition, the SPIO-M2pep based MHT can remodel the tumor immune microenvironment (TIME). The multifunctional SPIO-M2pep with M2 macrophage-targeting ability, high magnetic hyperthermia efficiency, MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

肿瘤相关巨噬细胞（TAM）在肿瘤的发展和进程中起着重要的作用。特别地，M2 TAM可通过促进肿瘤进展和恶性行为来促进肿瘤生长。选择性靶向消除M2 TAM以抑制肿瘤进展对癌症治疗具有重要意义。基于氧化铁纳米粒子的磁热疗（MHT）是破坏肿瘤组织深层穿透深度的经典方法。在这项研究中，我们开发了一种典型的M2巨噬细胞靶向肽（M2pep）功能化的超顺磁性氧化铁纳米颗粒（SPIO），用于原位乳腺癌小鼠模型中的磁共振成像（MRI）引导的MHT。所获得的水动力学直径为20 nm的多功能SPIO-M2pep显示出有效的靶向能力，高的横向弛豫性（149 mM^-1 s ^-1）和令人满意的体外磁疗性能。体内研究表明，基于SPIO-M2pep的MRI可以监测纳米颗粒在肿瘤中的分布，并指出进行MHT的合适时机。以M2巨噬细胞为靶点的MHT显着降低了肿瘤体积和肿瘤中M2 TAM的数量。此外，基于SPIO-M2pep的MHT可以重塑肿瘤免疫微环境（TIME）。具有M2巨噬细胞靶向能力，高磁热效率，MR成像功能以及重塑TIME的有效作用的多功能SPIO-M2pep具有改善临床癌症治疗结果的巨大潜力。