Polymeric nanoparticles encapsulating α-mangostin inhibit the growth and metastasis in colorectal cancer

Abstract α-Mangostin, the most abundant xanthone extracted from pericarp of mangosteen fruits, has been shown potential treatment effects in various cancer cell types. This led us to explore the anti-tumor activity and related mechanisms of α-mangostin in colorectal cancer. In this study, poly(ethylene glycol)–poly(e-caprolactone)–poly(ethylene glycol) (PEG–PCL–PEG, PECE) nanoparticles was used to encapsulate free α-mangostin, creating α-mangostin loaded PECE (α-M/PECE) nanoparticles. When compared with free α-mangostin, α-M/PECE induced a significantly more apoptosis of both CT26 and HCT116 cells in vitro, leading to an obviously more loss of mitochondrial membrane potential (Δψm) in HCT116 cells. Results of western blot assay and caspase-inhibiting assay showed that cell apoptosis induced by α-mangostin might via activating both death receptor-mediated caspase-8 pathway and mitochondrial dependent cytochrome c/caspase-9, with simultaneously regulating expression levels of Bcl-2 family proteins, and ultimately activating caspase-3. Moreover, the administration of α-M/PECE nanoparticles also exhibited significantly stronger inhibition in tumor growth, tumor angiogenesis, tumor cell proliferation as well as inducted more tumor cell apoptosis in subcutaneous xenograft models. Especially, α-M/PECE nanoparticles showed excellent anti-metastasis efficacy in both pulmonary metastasis model and abdominal metastasis model of colorectal cancer. The safety assessment also showed no obvious side effects were detected in mice which were treated with free α-mangostin or α-M/PECE nanoparticles. These results suggested the potential of α-M/PECE nanoparticles as an excellent intravenously injectable formulation of free α-mangostin for the treatment of colorectal cancer.