转移是一个涉及多种因素和阶段的复杂过程，其中肿瘤细胞和肿瘤微环境（TME）发挥着重要作用。针对肿瘤细胞和 TME 的口服生物可利用治疗剂的组合有利于预防或阻止转移的进展，尤其是在无法检测到的情况下。然而，依次克服肠道屏障、确保肿瘤和转移组织中的生物分布以及增强有效治疗所需的治疗效果仍然具有挑战性。受天然草药独特化学特性的启发，我们提出了一种口服草药-纳米颗粒混合系统（HNS），该系统通过桔梗-莪术 (HG)（临床实践中用于治疗乳腺癌转移的草药对/组）与负载水飞蓟宾的脂质聚合物纳米颗粒 (LPN) 的自结合。使用表面增强拉曼光谱评估了 HG 与 LPN 结合的分子结构，以进行 HNS 表面化学表征。此外，使用 UPLC-Orbitrap-MS/MS 鉴定了 HG 的分子类别，以进一步确认表面结合。分别使用体外多粒子追踪和环境响应荧光探针在 4T1 荷瘤小鼠中评估粘液扩散和体内生物分布。在 4T1 荷瘤小鼠中评估了乳腺癌转移的缓解情况，并研究了其潜在机制。与 LPN 相比，HNS 通过改变亲水性和表面特性来减少颗粒-粘液相互作用。小鼠体内 HNS 的上皮运输和通过派尔氏淋巴集结的吸收得到改善，促进其在肺和肿瘤组织中的生物分布。此外，HNS 通过诱导细胞凋亡和调节 MMP-9 和 TGF-β1 的表达来减轻肺转移，从而改变 4T1 荷瘤小鼠的 TME。HNS 提供了一个有吸引力的系统，具有多成分结合的草药，以促进口服纳米颗粒递送效率和肺转移的减轻。这一策略可能有助于改善乳腺癌患者的治疗。© 2024 Shi 等人。

Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC-Orbitrap-MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.The HNS reduced particle-mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer's patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β1, which altered the TME in 4T1 tumor-bearing mice.HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.© 2024 Shi et al.