Cai Yuxin, Kang Xuejia, Zhou Lang, Wu Shuai, Wang Chuanyu, Wu Siqi, Huang Chunghui, Wang Qi, Chang Ya, Babu R Jayachandra, Chen Pengyu
Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, Alabama 36849, USA.
Harrison College of Pharmacy, Auburn University, Auburn, Alabama 36849, USA.
Adv Funct Mater. 2025 Mar 28. doi: 10.1002/adfm.202425286.
Aggressive cancers, characterized by high metastatic potential and resistance to conventional therapies, present a significant challenge in oncology. Current treatments often fail to effectively target metastasis, recurrence, and the immunosuppressive tumor microenvironment, while causing significant off-target toxicity. Here, we present superparamagnetic copper iron oxide nanoparticles (SCIONs) as a multifunctional platform that integrates magnetic hyperthermia therapy, immune modulation, and targeted chemotherapeutic delivery, aiming to provide a more comprehensive cancer treatment. Specifically, SCIONs generate localized hyperthermia under an alternating magnetic field while delivering a copper-based anticancer agent, resulting in a synergistic anticancer effect. The hyperthermia induced by SCIONs caused ER stress and ROS production, leading to significant tumor cell death, while the copper complex further enhanced oxidative stress, ferroptosis, and apoptosis. Beyond direct cytotoxicity, SCIONs disrupted the tumor microenvironment by inhibiting cancer-associated fibroblasts, downregulating epithelial-mesenchymal transition markers, and reducing cell migration and invasion, thereby limiting metastasis. Additionally, SCION-based therapy reprogrammed the immune microenvironment by inducing immunogenic cell death and enhancing dendritic cell activation, resulting in increased CD8+ T cell infiltration and amplified antitumor immunity. This integrated approach targets primary and metastatic tumors while mitigating immunosuppression, offering a promising next-generation therapy for combating cancer with enhanced efficacy and reduced side effects.
侵袭性癌症具有高转移潜能且对传统疗法耐药，给肿瘤学带来了重大挑战。当前的治疗方法往往无法有效靶向转移、复发以及免疫抑制性肿瘤微环境，同时还会导致显著的脱靶毒性。在此，我们提出超顺磁性铜铁氧化物纳米颗粒（SCIONs）作为一种多功能平台，它整合了磁热疗、免疫调节和靶向化疗药物递送，旨在提供一种更全面的癌症治疗方法。具体而言，SCIONs在交变磁场下产生局部高温，同时递送一种铜基抗癌剂，从而产生协同抗癌效果。SCIONs诱导的高温引起内质网应激和活性氧生成，导致大量肿瘤细胞死亡，而铜络合物进一步增强氧化应激、铁死亡和细胞凋亡。除了直接的细胞毒性外，SCIONs通过抑制癌症相关成纤维细胞、下调上皮-间质转化标志物以及减少细胞迁移和侵袭来破坏肿瘤微环境，从而限制转移。此外，基于SCIONs的疗法通过诱导免疫原性细胞死亡和增强树突状细胞活化来重新编程免疫微环境，导致CD8 + T细胞浸润增加和抗肿瘤免疫力增强。这种综合方法靶向原发性和转移性肿瘤，同时减轻免疫抑制，为对抗癌症提供了一种有前景的下一代疗法，具有更高的疗效和更低的副作用。
