雜志名稱：Biomaterials
影響因子：14.0
文章題目：Mild magnetic hyperthermia-activated immuno-responses for primary bladder cancer therapy
DOI：10.1016/j.biomaterials.2024.122514
第一作者：Fenggang Qi，Qunqun Bao，Ping Hu，Yuedong Guo，Yang Yan，Xudong Yao，Jianlin Shi
作者單位：
中國科學院上海硅酸鹽研究所高性能陶瓷與超微結(jié)構(gòu)國家重點實驗室
中國科學院大學材料科學與光電子工程中心
同濟大學醫(yī)學院上海市第十人民醫(yī)院
同濟大學醫(yī)學院泌尿腫瘤研究所
中國醫(yī)學科學院納米催化醫(yī)學重點實驗室
引用YOBIBIO產(chǎn)品：
U21-265B DMEM高糖培養(yǎng)基
U21-279B RPMI1640
U21-259B PBS ph7.4
U31-322C 0.25%胰蛋白酶-EDTA消化液Trypsin-EDTA(1X),Liquid
U31-301C Penicillin Streptomycin（雙抗100X，青鏈霉素混合液）
U11-020A 優(yōu)級胎牛血清
U96-1626E Rat TNFα ELISA Kit
U96-1474E Rat IFNγ ELISA Kit
U96-1614E Rat TGFβ1 ELISA Kit
U96-1518E Rat IL-10 ELISA Kit
文章摘要：
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.
手術干預后化療是膀胱癌的主要治療策略，但手術風險大、化療毒性大、術后復發(fā)率高，阻礙了膀胱癌的治療。在此背景下，首次提出了一種通過膀胱內(nèi)輸送磁性納米顆粒來使用溫和磁熱療法（MHT）治療膀胱癌的新方法。該方法克服了與傳統(tǒng)靜脈注射磁性納米粒子相關的磁熱效率低、腫瘤靶向性不足以及治療效果降低的局限性。開發(fā)了核殼Zn-CoFeO@Zn-MnFeO（MNP）納米顆粒，并用透明質(zhì)酸（HA）進一步修飾，以增強其對腫瘤細胞的靶向能力。在 43-44 °C 溫度下使用 MNP-HA 進行受控溫和 MHT 成功抑制了膀胱腫瘤細胞的增殖和腫瘤生長，同時還降低了熱休克蛋白 70 (HSP70) 的表達水平。至關重要的是，這種治療方法還激活了人體涉及巨噬細胞的先天免疫反應，以及樹突狀細胞（DC）和T細胞的適應性免疫反應，從而逆轉(zhuǎn)膀胱腫瘤的免疫抑制環(huán)境，有效減少腫瘤復發(fā)。本研究揭示了輕度MHT治療膀胱癌的潛在免疫激活機制，并證實了該策略的有效性和安全性，表明其在高復發(fā)傾向膀胱癌的臨床治療中具有廣闊的前景。
