Shi Jiangpei, Zhang Rongguang, Wang Yu, Sun Yingwei, Gu Xiaoyan, An Yu, Chai Xinyu, Wang Xiaoyu, Wang Zhi, Lyu Yaqi, Guo Teng, Feng Nianping, Liu Ying
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Int J Nanomedicine. 2024 Aug 2;19:7927-7944. doi: 10.2147/IJN.S463657. eCollection 2024.
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 - (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.
转移是一个涉及多个因素和阶段的复杂过程，其中肿瘤细胞和肿瘤微环境（TME）起着重要作用。联合使用口服生物可利用的治疗药物靶向肿瘤细胞和TME，有助于预防或阻碍转移的进展，尤其是在转移难以察觉时。然而，依次克服肠道屏障、确保在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），该系统通过临床实践中用于治疗乳腺癌转移的药对/组方-（HG）与负载水飞蓟宾的脂质-聚合物纳米颗粒（LPNs）自组装形成。使用表面增强拉曼光谱对HNS表面化学进行表征，评估负责HG与LPNs结合的分子结构。此外，使用超高效液相色谱-轨道阱串联质谱（UPLC-Orbitrap-MS/MS）鉴定HG的分子类别，以进一步确认表面结合。分别使用体外多颗粒跟踪和环境响应荧光探针在4T1荷瘤小鼠中评估黏液扩散和体内生物分布。在4T1荷瘤小鼠中评估乳腺癌转移的缓解情况，并研究其潜在机制。
与LPNs相比，HNS通过改变亲水性和表面特性减少了颗粒与黏液的相互作用。HNS在小鼠中的上皮转运和通过派尔集合淋巴结的吸收得到改善，促进了它们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基质金属蛋白酶-9（MMP-9）和转化生长因子-β1（TGF-β1）的表达减轻了肺转移，这改变了4T1荷瘤小鼠的TME。
HNS提供了一个具有草药多组分结合的有吸引力的系统，以促进口服纳米颗粒递送效率和减轻肺转移。这种策略可能有助于改善乳腺癌患者的治疗。
