背景：铁基纳米载体已证明具有将肿瘤相关巨噬细胞 (TAM) 极化转向 M1 表型的潜力，这对于激活三阴性乳腺癌 (TNBC) 中的肿瘤微环境 (TME) 至关重要。然而，它们在现实世界中的有效性因 Fe2/3 暴露不足和肿瘤中缺乏合适的增效剂而受到限制。方法：我们引入了一种嵌入气囊的铁基 MIL-101 金属有机框架 (MOFMIL-101(Fe))，用于通过气泡驱动的 Fe2 /3 和香菇多糖的肿瘤共传递来点燃 TNBC 中的 TME。该系统命名为HM/Ef/LNT-MOFMIL-101(Fe)，以纳米级MOFMIL-101(Fe)为核心，嵌入NaHCO3作为pH触发的气囊，静电吸附的香菇多糖形成内壳，和一个带4T1的屏蔽壳

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.© The author(s).