Surgical intervention followed by chemotherapy is the principal treatment strategy for bladder cancer, which is hindered by significant surgical risks, toxicity from chemotherapy, and high rates of recurrence after surgery. In this context, a novel approach using mild magnetic hyperthermia therapy (MHT) for bladder cancer treatment through the intra-bladder delivery of magnetic nanoparticles is presented for the first time. This method overcomes the limitations of low magnetic thermal efficiency, inadequate tumor targeting, and reduced therapeutic effectiveness associated with the traditional intravenous administration of magnetic nanoparticles. Core-shell Zn–CoFeO@Zn–MnFeO (MNP) nanoparticles were developed and further modified with hyaluronic acid (HA) to enhance their targeting ability toward tumor cells. The application of controlled mild MHT using MNP-HA at temperatures of 43–44 °C successfully suppressed the proliferation of bladder tumor cells and tumor growth, while also decreasing the expression levels of heat shock protein 70 (HSP70). Crucially, this therapeutic approach also activated the body's innate immune response involving macrophages, as well as the adaptive immune responses of dendritic cells (DCs) and T cells, thereby reversing the immunosuppressive environment of the bladder tumor and effectively reducing tumor recurrence. This study uncovers the potential immune-activating mechanism of mild MHT in the treatment of bladder cancer and confirms the effectiveness and safety of this strategy, indicating its promising potential for the clinical management of bladder cancer with a high tendency for relapse.

中文翻译：

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原发性膀胱癌治疗的轻度磁热疗激活免疫反应

手术干预后化疗是膀胱癌的主要治疗策略，但手术风险大、化疗毒性大、术后复发率高，阻碍了膀胱癌的治疗。在此背景下，首次提出了一种通过膀胱内输送磁性纳米颗粒来使用温和磁热疗法（MHT）治疗膀胱癌的新方法。该方法克服了与传统静脉注射磁性纳米粒子相关的磁热效率低、肿瘤靶向性不足以及治疗效果降低的局限性。开发了核壳Zn-CoFeO@Zn-MnFeO（MNP）纳米颗粒，并用透明质酸（HA）进一步修饰，以增强其对肿瘤细胞的靶向能力。在 43-44 °C 温度下使用 MNP-HA 进行受控温和 MHT 成功抑制了膀胱肿瘤细胞的增殖和肿瘤生长，同时还降低了热休克蛋白 70 (HSP70) 的表达水平。至关重要的是，这种治疗方法还激活了人体涉及巨噬细胞的先天免疫反应，以及树突状细胞（DC）和T细胞的适应性免疫反应，从而逆转膀胱肿瘤的免疫抑制环境，有效减少肿瘤复发。本研究揭示了轻度MHT治疗膀胱癌的潜在免疫激活机制，并证实了该策略的有效性和安全性，表明其在高复发倾向膀胱癌的临床治疗中具有广阔的前景。