Co-delivery of bufalin and nintedanib via albumin sub-microspheres for synergistic cancer therapy

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.