气囊安装的MIL-101（FE）金属有机框架，用于通过战略性地输送铁离子和扁豆，用于放大的肿瘤微环境激活环
Air bag-embedded MIL-101(Fe) metal-organic frameworks for an amplified tumor microenvironment activation loop through strategic delivery of iron ions and lentinan
影响因子:13.30000
分区:医学1区 Top / 医学：研究与实验1区
发表日期:2024
作者:
Tao Han, Yan Sun, Xi Jiang, Chengming Gong, Fei Kong, Yi Luo, Chang Ge, Congyan Liu, Yuping Liu, Yanfei Mou, Huangqin Zhang, Jianming Ju, Yan Chen, Ding Qu
摘要
背景：基于铁的纳米载体在将肿瘤相关的巨噬细胞（TAM）极化转向M1表型方面具有潜力，对于激活三阴性乳腺癌（TNBC）中肿瘤微环境（TME）至关重要。但是，由于Fe2+/3+暴露不足以及在肿瘤中缺乏合适的协同作用，它们的现实世界有效性会减少。方法：我们引入了一个基于气囊的铁基MIL-101金属有机框架（MOFMIL-101（FE）），用于通过泡沫驱动的FE2+/3+和Lentinan的肿瘤造成的肿瘤代码来点燃TNBC中的TME。该系统名为HM/EF/LNT-MOFMIL-101（Fe），以纳米尺寸的Mofmil-101（Fe）为核心，作为核心，嵌入了Nahco3作为pH触发的气袋，静电添加的Lentinan，形成了内壳，形成了Inner Shell，并带有4T1＆Red Flood Cell Cell Cell Cell Cell Blood Blood Bloodbrane heaild壳。结果：HM/EF/LNT-MOFMIL-101（Fe）可以减轻血液中的非特异性捕获，但对酸性肿瘤环境有反应，迅速产生一系列CO2气泡以拆卸MOFMIL-101（FE）。进入肿瘤后，纵南扬丹诱导的干扰素-γ（IFN-γ）促进Fe2+/3+促进增强的趋前和芬顿样反应，从而通过“ IFN-γ-γ-feRoptosis-Ros-caspase-3”途径将TAM推向M1极化。此外，HM/EF/LNT-MOFMIL-101（Fe）增加了T淋巴细胞的浸润并减少调节T细胞。这些级联免疫反应协同促进了基于TAMS M1极化的放大TME激活的环路，展示了抗癌有效性方面的显着进步和各种组合疗法的希望。结论：这项研究采用了“嵌入式空气袋”策略来实现Fe2+/3+和Lentinan的战略性代码交付，为TME提供了一种新工具。
Abstract
Background: Iron-based nanocarriers have demonstrated potential in redirecting tumor associated macrophages (TAMs) polarization towards the M1 phenotype, critical for activating the tumor microenvironment (TME) in triple negative breast cancer (TNBC). However, their real-world effectiveness is curtailed by insufficient Fe2+/3+ exposure and the absence of suitable synergists in tumors. Methods: We introduce an air bag-embedded iron-based MIL-101 metal-organic frameworks (MOFMIL-101(Fe)) for igniting the TME in TNBC through bubble-driven tumoral codelivery of Fe2+/3+ and lentinan. This system, named HM/Ef/LNT-MOFMIL-101(Fe), features nano-sized MOFMIL-101(Fe) as the core, embedded NaHCO3 as a pH-triggered air bag, electrostatically-adsorbed lentinan forming the inner shell, and a shield shell with 4T1&red blood cell hybrid membrane. Results: HM/Ef/LNT-MOFMIL-101(Fe) can mitigate non-specific capture in the bloodstream but respond to the acidic tumor milieu, rapidly generating a burst of CO2 bubbles to disassemble MOFMIL-101(Fe). Upon entering tumors, lentinan-induced interferon-γ (IFN-γ) enable Fe2+/3+ facilitating an enhanced ferroptosis and Fenton-like reaction, pushing TAMs towards M1 polarization via the "IFN-γ-ferroptosis-ROS-Caspase-3" pathway. Moreover, HM/Ef/LNT-MOFMIL-101(Fe) increases the infiltration of T lymphocytes and decreases regulatory T cells. These cascading immune responses synergistically foster a loop of amplified TME activation based on TAMs M1 polarization, showcasing notable advancements in anticancer effectiveness and promise for various combination therapies. Conclusion: This study utilizes an "embedded air-bag" strategy to achieve strategic codelivery of Fe2+/3+ and lentinan, providing a new tool for engineering the TME.