A donut-shaped nanostructure that can effectively approach lung metastasis and offer a burst penetrative delivery to overcome tumor heterogeneity has been proposed. The intravenously injected donut serves as a tumor-adhesion agent via the margination effect and hierarchical donut-shaped nanostructure, which drives nanoparticle-induced extracellular leakiness (nanoEL) both in vitro and in vivo. In an animal metastasis model, more than 72% of donuts localize to lung metastatic tumors instead of normal tissues. Upon the application of a high-frequency magnetic field (MF), a burst generation of polydox (pDox) particles from the carbon porous reservoirs of donuts enhances the retention in the deep tumor, facilitating penetrative delivery. Via pH-responsive hydrozone bonds, the penetrative pDox particles are cleaved into doxorubicin (Dox), yielding high intracellular concentrations of activated Dox at the tumor. The donut-shaped nanostructure loaded with pDox improved the survival rates in a mouse model of metastatic lung cancer and the activity of immune response.

中文翻译：

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由PolyDox产生介导的穿透性递送至深部肿瘤的边缘效应穿梭的靶向肺转移的甜甜圈状纳米结构

已经提出了一种甜甜圈状的纳米结构，该结构可以有效地处理肺转移并提供爆发性穿透递送，以克服肿瘤的异质性。在静脉内注射甜甜圈用作肿瘤粘连剂经由所述边集效果和分层环形的纳米结构，其中纳米颗粒驱动诱导细胞外泄漏（nanoEL）二者在体外和体内。在动物转移模型中，超过72％的甜甜圈定位于肺转移性肿瘤而不是正常组织。施加高频磁场（MF）后，从甜甜圈的碳多孔储层中突然产生多氧化二磷（pDox）颗粒，从而增强了其在深部肿瘤中的保留能力，从而促进了渗透性传递。通过pH响应的氢键，将穿透性pDox颗粒裂解为阿霉素（Dox），从而在肿瘤中产生高细胞内激活Dox浓度。装有pDox的甜甜圈形纳米结构提高了转移性肺癌小鼠模型的存活率和免疫反应活性。