Preventing cancer metastasis is one of the remaining challenges in cancer therapy. As an efficient natural product, alpha-tocopheryl succinate (α-TOS), the most effective form of vitamin E, holds great anticancer potential. To improve its efficacy and bioavailability, lipid-coated calcium carbonate/phosphate (LCCP) nanoparticles (NPs) with folic acid and PEG modification are synthesized for efficient delivery of α-TOS to 4T1 cancer cells. The optimized LCCP-FA NPs (NP-TOS15) show an α-TOS loading efficiency of around 60%, and enhanced uptake by 4T1 metastatic cancer cells. Consequently, NP-TOS15 significantly enhance the anticancer effect in combination with interferon-gamma (IFN-γ) in terms of apoptosis facilitation and migration inhibition. Importantly, NP-TOS15 upregulate the anticancer immunity via downregulating program death ligand 1 (PD-L1) expression that is initially induced by IFN-γ, and remarkably prevent the lung metastasis, particularly in combination with IFN-γ. Further investigation reveals that this combination therapy also modulates the cytotoxic lymphocyte infiltration into the tumor microenvironment for tumor elimination. Taken together, the NP delivery of α-TOS in combination with IFN-γ provides an applicable strategy for cancer therapy.

中文翻译：

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通过纳米颗粒递送的维生素 E 与干扰素-γ 的结合增强预防乳腺肿瘤转移。

预防癌症转移是癌症治疗中剩下的挑战之一。作为一种高效的天然产物，α-生育酚琥珀酸酯 (α-TOS) 是维生素 E 的最有效形式，具有巨大的抗癌潜力。为了提高其功效和生物利用度，合成了具有叶酸和 PEG 修饰的脂质包覆的碳酸钙/磷酸钙 (LCCP) 纳米颗粒 (NPs)，用于将 α-TOS 有效递送至 4T1 癌细胞。优化的 LCCP-FA NPs (NP-TOS15) 显示出约 60% 的 α-TOS 负载效率，并增强了 4T1 转移性癌细胞的摄取。因此，就凋亡促进和迁移抑制而言，NP-TOS15 与干扰素-γ (IFN-γ) 联合使用可显着增强抗癌作用。重要的，NP-TOS15 通过下调最初由 IFN-γ 诱导的程序死亡配体 1 (PD-L1) 的表达来上调抗癌免疫，并显着预防肺转移，特别是与 IFN-γ 联合使用。进一步的研究表明，这种联合疗法还可以调节细胞毒性淋巴细胞浸润到肿瘤微环境中以消除肿瘤。总之，α-TOS 的 NP 递送与 IFN-γ 结合为癌症治疗提供了一种适用的策略。