Albumin nanoparticles represent an approved anti-tumor drug delivery system. However, there is only one albumin nanoparticle product (paclitaxel-albumin nanoparticle) on the market. The application of albumin carriers is limited by the lack of universal preparation technology and insufficient targeting effect. Herein, we developed multifunctional albumin sub-microspheres prepared by coaxial-electrospray technology to co-delivery bufalin and nintedanib for tumor-targeted combination therapy. The biguanide and ursodeoxycholic acid dual-modified multifunctional albumin was synthesized to enhance the anti-tumor effect and tumor target efficiency. Coaxial-electrospray technology was utilized in preparing albumin sub-microspheres with a core-shell structure that enables payload efficiency and stability. More importantly, the in vitro and in vivo experiments demonstrated that the multifunctional albumin sub-microspheres possessed superior tumor target efficiency. Furthermore, nintedanib and bufalin combined therapy relieved the tumor microenvironment and exerted a synergistic therapeutic effect. Therefore, this work provides a novel method for fabricating an albumin-based drug delivery system and a potential efficient combination therapeutic strategy for tumor treatment.

白蛋白纳米颗粒代表一种经批准的抗肿瘤药物递送系统。然而，市场上只有一种白蛋白纳米颗粒产品（紫杉醇-白蛋白纳米颗粒）。白蛋白载体的应用受限于缺乏通用的制备技术和靶向效果不足。在此，我们开发了通过同轴电喷雾技术制备的多功能白蛋白亚微球，用于共同递送布法林和尼达尼布，用于肿瘤靶向联合治疗。合成双胍和熊去氧胆酸双重修饰的多功能白蛋白，增强抗肿瘤作用和肿瘤靶向效率。同轴电喷雾技术用于制备具有核壳结构的白蛋白亚微球，可提高有效载荷的效率和稳定性。更重要的是，体外和体内实验表明，多功能白蛋白亚微球具有优异的肿瘤靶向效率。此外，尼达尼布与布法林联合治疗可缓解肿瘤微环境，发挥协同治疗作用。因此，这项工作为制造基于白蛋白的药物递送系统提供了一种新方法，并为肿瘤治疗提供了一种潜在的有效联合治疗策略。