Self-assembling nanoarchitectonics of size-controllable celastrol nanoparticles for efficient cancer chemotherapy with reduced systemic toxicity

Celastrol, extracted from Tripterygium wilfordii Hook F, is one of the most promising natural extract for cancer treatment. Nevertheless, insufficient tumor retention and severe systemic toxicity still hinder its application. Herein, we report for the first time that Celastrol can directly self-assemble into sizecontrollable nanoparticles through the anti-solvent method by using different good solvent or by the variation of Celastrol concentrations. In vitro anti-cancer experiment revealed that the as-prepared nanoparticles can kill MCF-7 cells more effectively. Moreover, the nanoparticles can efficiently accumulate in tumors of the tumor bearing mice after tail vein injection. Under the administration of lethal dosage of Celastrol, the tumors are greatly suppressed and the mice maintain the activity. These results demonstrate that anti-solvent method may be a promising strategy to fabricate Celastrol nano-drugs with controllable size and less systemic toxicity for further clinical cancer treatment.(c) 2022 Published by Elsevier Inc.

Automated summary

This study reports, for the first time, that Celastrol can self-assemble into size-controllable nanoparticles via the anti-solvent method using different solvents or varying Celastrol concentrations. In vitro experiments showed that the prepared nanoparticles can effectively kill MCF-7 cells. Furthermore, the nanoparticles can accumulate efficiently in tumors after intravenous injection. Administration of a lethal dosage of Celastrol resulted in significant tumor suppression with maintained activity in mice. These findings suggest that the anti-solvent method holds promise for fabricating Celastrol nano-drugs with controlled size and reduced systemic toxicity for clinical cancer treatment.