Preparation of polydopamine-modified celastrol nanosuspension and its anti-liver cancer activity in vitro

Abstract

Celastrol (CEL) is one of the main effective components of traditional Chinese medicine Tripterygium wilfordii Hook.f, which has high antitumor activity. However, its low solubility and low bioavailability limit its clinical use. In this study, a CEL nanosuspension (PDA@CEL-NS) with near-infrared photothermal properties was prepared. PDA@CEL-NS contained spherical nanoparticles with an average particle size of 189.67 nm, zeta potential of −30.23 mV, and 60.33% drug loading. X-ray diffraction showed that PDA@CEL-NS had an amorphous structure. PDA@CEL-NS had good stability after storage at 4 °C and 37 °C for 30 days, and there was no aggregation or sedimentation in a 5% glucose solution or culture medium. The highly dispersed nanoparticles greatly improved dissolution in vitro, and the cumulative release rate of PDA@CEL-NS over 72 h was as high as 60.10%. It demonstrated both high release and a good sustained-release effect. Cell experiments showed that PDA@CEL-NS had stronger efficacy than CEL-NS or CEL, and the efficacy was further enhanced after laser application. Nuclear rupture and deformation and the induction of apoptosis were potential toxic mechanisms, and they also inhibited cell migration. In conclusion, PDA@CEL-NS is expected to become a nano-drug delivery system for the treatment of cancer.