Flower-like Composite Material Delivery of Co-Packaged Lenvatinib and Bufalin Prevents the Migration and Invasion of Cholangiocarcinoma.

The co-delivery of multiple drugs using nanocarriers has been recognized as a promising strategy for cancer treatment to enhance therapeutic efficacy. In this study, a monodisperse mesoporous silica nanoparticle (mSiO) is prepared and functionalized into high-efficiency loaded Lenvatinib and Bufalin for targeted delivery to Cholangiocarcinoma (CCA). mSiO was synthesized on solid silica nanoparticles by oil-water interface method, and highly monodisperse mSiO with uniform morphology was obtained. mSiO was then sequentially modified by polyethylene glycol (PEG) and the targeting molecule folic acid (FA). mSiO-FA was designed as co-delivery system for Lenvatinib (Le) and Bufalin (Bu) to increase drug availability and highly target tumor cells. Compared with unfunctionalized mSiO, mSiO-FA can more efficiently enter human CCA cell lines (9810 cells) and enhance intracellular drug delivery. Moreover, drug-loaded mSiO-FA (Le/Bu@mSiO-FA) significantly inhibited the viability, migration and invasion of 9810 cells. In vivo, the nanocomplex significantly reduced the tumor load in CCA tumor-bearing mouse models compared to Le or Bu alone. The current work provides a useful strategy for highly targeted and multidrug-resistance reversal therapy for CCA.