Qi Fenggang, Bao Qunqun, Hu Ping, Guo Yuedong, Yan Yang, Yao Xudong, Shi Jianlin
State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai, 200050, PR China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Shanghai Tenth People's Hospital, Medical School of Tongji University, 38 Yun-xin Road, Shanghai, 200435, PR China.
Biomaterials. 2024 Jun;307:122514. doi: 10.1016/j.biomaterials.2024.122514. Epub 2024 Feb 21.
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.
手术干预后进行化疗是膀胱癌的主要治疗策略,但该策略受到重大手术风险、化疗毒性以及术后高复发率的阻碍。在此背景下,首次提出了一种通过膀胱内递送磁性纳米颗粒,利用温和磁热疗(MHT)治疗膀胱癌的新方法。该方法克服了传统静脉注射磁性纳米颗粒所带来的磁热效率低、肿瘤靶向性不足以及治疗效果降低等局限性。开发了核壳结构的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进行可控温和磁热疗,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机体涉及巨噬细胞的固有免疫反应,以及树突状细胞(DC)和T细胞的适应性免疫反应,从而逆转了膀胱肿瘤的免疫抑制环境,有效降低了肿瘤复发率。本研究揭示了温和磁热疗在治疗膀胱癌中的潜在免疫激活机制,并证实了该策略的有效性和安全性,表明其在临床治疗高复发倾向膀胱癌方面具有广阔的应用前景。
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