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(guó)科學(xué)院上海硅酸鹽研究所高性能陶瓷與超微結(jié)構(gòu)國(guó)家重點(diǎn)實(shí)驗(yàn)室
中國(guó)科學(xué)院大學(xué)材料科學(xué)與光電子工程中心
同濟(jì)大學(xué)醫(yī)學(xué)院上海市第十人民醫(yī)院
同濟(jì)大學(xué)醫(yī)學(xué)院泌尿腫瘤研究所
中國(guó)醫(yī)學(xué)科學(xué)院納米催化醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)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(jí)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(shù)干預(yù)后化療是膀胱癌的主要治療策略，但手術(shù)風(fēng)險(xiǎn)大、化療毒性大、術(shù)后復(fù)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(guān)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(jìn)一步修飾，以增強(qiáng)其對(duì)腫瘤細(xì)胞的靶向能力。在 43-44 °C 溫度下使用 MNP-HA 進(jìn)行受控溫和 MHT 成功抑制了膀胱腫瘤細(xì)胞的增殖和腫瘤生長(zhǎng)，同時(shí)還降低了熱休克蛋白 70 (HSP70) 的表達(dá)水平。至關(guān)重要的是，這種治療方法還激活了人體涉及巨噬細(xì)胞的先天免疫反應(yīng)，以及樹突狀細(xì)胞（DC）和T細(xì)胞的適應(yīng)性免疫反應(yīng)，從而逆轉(zhuǎn)膀胱腫瘤的免疫抑制環(huán)境，有效減少腫瘤復(fù)發(fā)。本研究揭示了輕度MHT治療膀胱癌的潛在免疫激活機(jī)制，并證實(shí)了該策略的有效性和安全性，表明其在高復(fù)發(fā)傾向膀胱癌的臨床治療中具有廣闊的前景。
