在临床化疗中，白蛋白包裹型紫杉醇（Abraxane）可以改善紫杉醇（PTX）针对原位恶性肿瘤的肿瘤靶向性和治疗效果。然而，转移性癌症患者预后差，可能是由于白蛋白包裹型紫杉醇的不稳定性、化疗抵抗性和无法改变肿瘤微环境。在这里，我们提出了一种新的双胍修饰的基于白蛋白的纳米平台，用于包裹紫杉醇以有效治疗转移性癌症。紫杉醇包裹在聚（乳酸-聚乙二醇酸）核心中，外覆双胍修饰的白蛋白（HSA-NH）。功能化纳米颗粒（HSA-NH NPs）表现出显著稳定的特性，低药物释放（P < 0.05，与Abraxane相比），靶向肿瘤组织，抑制上皮间质转化（EMT）事件以实现抗转移效果，并减少癌细胞干细胞的表型。结果表明，HSA-NH NPs通过抑制原发肿瘤生长和转移，有效延长动物生存期（55天）。本研究证明，双胍锚定的基于白蛋白的纳米平台包裹紫杉醇是治疗转移性癌症的一种有效、安全和临床转化策略。研究意义声明：白蛋白包裹型紫杉醇（Abraxane）可以增加紫杉醇在乳腺癌等临床癌症治疗中的肿瘤靶向性和治疗效果。然而，白蛋白包裹型紫杉醇的不稳定性、化疗抵抗性以及无法改变肿瘤微环境可能导致转移性癌症患者治疗效果差。在这里，我们开发了锚定双胍的基于白蛋白的纳米平台来包裹紫杉醇（HSA-NH NPs）以治疗转移性癌症。聚（乳酸-聚乙二醇酸）（PLGA）核心中包裹紫杉醇可以改善HSA-NH NPs的稳定性。基于二甲双胍的活性，锚定在PLGA核心上的双胍修饰的白蛋白可以提高紫杉醇的疗效，抑制上皮间质转化过程中的各种异常变化，并减少肿瘤细胞干性。锚定双胍的基于白蛋白的纳米平台包裹紫杉醇可作为一种强大、安全和临床转化的转移性癌症治疗方法。版权所有 © 2023 Elsevier Ltd.

In clinical chemotherapy, albumin-bound paclitaxel (Abraxane) can improve the tumor targeting property and therapeutic efficacy of paclitaxel (PTX) against orthotopic malignancies. However, patients with metastatic cancer have a poor prognosis, probably due to the instability, chemoresistance, and inability of albumin-bound paclitaxel to alter the tumor microenvironment. Here we propose a new biguanide-modified albumin-based nanoplatform that encapsulates paclitaxel for the effective treatment of metastatic cancer. The PTX is encapsulated in poly (lactic-co-glycolic acid) cores coated with biguanide-modified albumin (HSA-NH). The functionalized nanoparticles (HSA-NH NPs) exhibit a remarkable stable profile with low drug release (P < 0.05 versus Abraxane), target tumor tissues, suppress epithelial-mesenchymal transition (EMT) events for anti-metastatic effects, and reduce the phenotype of cancer stem cells. As a result, HSA-NH NPs effectively prolong animal survival (55 days) by inhibiting not only primary tumor growth but also metastasis. This study provides proof of concept that the biguanide-anchored albumin-based nanoplatform encapsulating PTX is a powerful, safe, and clinically translational strategy for the treatment of metastatic cancer. STATEMENT OF SIGNIFICANCE: Albumin-bound paclitaxel (Abraxane) can increase paclitaxel's tumor targeting and therapeutic efficacy in clinical cancer treatments such as breast cancer. However, the instability, chemoresistance, and lack of tumor microenvironment modulation of albumin-bound paclitaxel may lead to poor therapeutic efficacy in metastatic cancer patients. Here we develop biguanide-anchored albumin-based nanoplatforms that encapsulate paclitaxel (HSA-NH NPs) for metastatic cancer treatment. Poly(lactic-co-glycolic acid) (PLGA) cores encapsulating paclitaxel improve the stability of HSA-NH NPs. Based on the activities of metformin, biguanide-anchored albumin adsorbed on PLGA cores improves paclitaxel efficacy, inhibits various aberrant changes during epithelial-mesenchymal transition, and reduces tumor cell stemness. The biguanide-anchored albumin-based nanoplatform encapsulating PTX can serve as a potent, safe, and clinically translational approach for metastatic cancer therapies.Copyright © 2023. Published by Elsevier Ltd.