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

Abstract

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 (mSiO2) is prepared and functionalized into high-efficiency loaded Lenvatinib and Bufalin for targeted delivery to Cholangiocarcinoma (CCA). mSiO2 was synthesized on solid silica nanoparticles by oil–water interface method, and highly monodisperse mSiO2 with uniform morphology was obtained. mSiO2 was then sequentially modified by polyethylene glycol (PEG) and the targeting molecule folic acid (FA). mSiO2-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 mSiO2, mSiO2-FA can more efficiently enter human CCA cell lines (9810 cells) and enhance intracellular drug delivery. Moreover, drug-loaded mSiO2-FA (Le/Bu@mSiO2-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.

Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System

“…168,169 Most studies on NDDS-LVN have shown that LVN encapsulated in NDDS has similar hematology analysis results, liver and renal function compared with free LVN. 38,41,46,52 Histopathological examination revealed no organ injury or inflammation in NDDS-LVN treated animals compared to free LVN. Interestingly, one study showed lower cytotoxicity of LVN in NDDS at equal concentrations.…”

Bufalin-loaded vitamin E succinate-grafted chitosan oligosaccharide/RGD-conjugated TPGS mixed micelles inhibit intraperitoneal metastasis of ovarian cancer

“…The formation of nano-carriers is an effective way to improve the therapeutic effect of bufalin. Several studies have taken advantage of nano-drug delivery systems to target delivery of bufalin for enhance its antitumor therapy and attenuate toxicity, such as platelet membrane biomimetic nanoparticle, liposomes, polymeric prodrug, bovine serum albumin nanoparticle, monodisperse mesoporous silica nanoparticle, metal-organic frameworks(MOFs) and so on (Tian et al 2014;Ning et al 2022;Zeng et al 2021;Hu et al 2012;Wen et al 2017;Ettlinger et al 2022). Zeng et al designed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of bufalin (FA-MOF/Buf ), which could improve water solubility and stability, higher intracellular uptake, and enhanced antitumor effect of bufalin in breast cancer (Zeng et al 2021).…”

“…Zeng et al designed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of bufalin (FA-MOF/Buf ), which could improve water solubility and stability, higher intracellular uptake, and enhanced antitumor effect of bufalin in breast cancer (Zeng et al 2021). Ning et al prepared a monodisperse mesoporous silica nanoparticle to load lenvatinib and bufalin for targeted delivery to cholangiocarcinoma, which indicated a superior therapeutic effect than free drugs (Ning et al 2022). Compared with previously reported nano-drug delivery systems, VES-CSO/TPGS-RGD MMs are easier to prepare and more multifunctional.…”

Cypate‐loaded hollow mesoporous Prussian blue nanoparticle/hydrogel system for efficient photodynamic therapy/photothermal therapy dual‐modal antibacterial therapy

“…Moreover, we detect the hemolysis rate Cy-HMPBs and Cy-HMPBs/CH The results indicated that the hemolysis rate of all samples was lower than 1%, confirming the bio-safety of our therapeutic strategy (Figure 3H). 54 We then evaluated the photothermal capacity of Cy-HMPBs/CH.…”