Metastasis accounts for the majority of cancer deaths in many tumor types including breast cancer. Epithelial-mesenchymal transition (EMT) is the driving force for the occurrence and progression of metastasis, however, no targeted strategies to block the EMT program are currently available to combat metastasis. Diverse engineered nanomaterials (ENMs) have been reported to exert promising anti-cancer effects, however, no ENMs have been designed to target EMT. Palladium (Pd) nanomaterials, a type of ENM, have received substantial attention in nanomedicine due to their favorable photothermal performance for cancer therapeutics. Herein, Pd nanoplates (PdPL) were found to be preferentially biodistributed to both primary tumors and metastatic tumors. Importantly, PdPL showed a significant inhibition of lung metastasis with and without near-infrared (NIR) irradiation. Mechanistic investigations revealed that EMT was significantly compromised in breast cancer cells upon the PdPL treatment, which was partially due to the inhibition of the transforming growth factor-beta (TGF-β) signaling. Strikingly, the PdPL was found to directly interact with TGF-β proteins to diminish TGF-β functions in activating its downstream signaling, as evidenced by the reduced phosphorylation of Smad2. Notably, TGF-β-independent pathways were also involved in undermining EMT and other important biological processes that are necessary for metastasis. Additionally, NIR irradiation elicited synergistic effects on PdPL-induced inhibition of primary tumors and metastasis. In summary, these results revealed that the PdPL remarkably curbed metastasis by inhibiting EMT signaling, thereby indicating the promising potential of PdPL as a therapeutic agent for treating breast cancer metastasis.
转移是包括乳腺癌在内的多种肿瘤类型中导致癌症死亡的主要原因。上皮-间质转化是转移发生和进展的驱动力，然而目前尚无针对阻断该过程的靶向策略可用于对抗转移。多种工程化纳米材料已被报道具有潜在的抗癌效果，但尚无专门针对上皮-间质转化的纳米材料设计。钯纳米材料作为一种工程化纳米材料，因其在癌症治疗中优越的光热性能而在纳米医学领域受到广泛关注。本研究发现钯纳米片能够优先生物分布于原发肿瘤和转移瘤中。重要的是，无论近红外照射与否，钯纳米片均对肺转移表现出显著抑制作用。机制研究表明，钯纳米片处理能显著破坏乳腺癌细胞的上皮-间质转化过程，这部分归因于其对转化生长因子-β信号通路的抑制。引人注目的是，钯纳米片被发现可直接与转化生长因子-β蛋白相互作用，削弱其激活下游信号传导的功能，Smad2磷酸化水平降低证实了这一点。值得注意的是，独立于转化生长因子-β的途径也参与了破坏上皮间质转化及其他转移必需的重要生物过程。此外，近红外照射对钯纳米片诱导的原发肿瘤和转移抑制产生了协同效应。综上所述，这些结果表明钯纳米片通过抑制上皮-间质转化信号通路显著抑制转移，从而显示出钯纳米片作为治疗乳腺癌转移疗剂的巨大潜力。
肿瘤(癌症)患者之家