Biomimetic celastrol nanocrystals with enhanced efficacy and reduced toxicity for suppressing breast cancer invasion and metastasis.

Breast cancer and its lung metastases pose significant threats to women's health worldwide, impacting their quality of life. Although several therapeutic strategies against breast cancer have been developed, they often cause serious side effects due to their high toxicity and low specificity. Therefore, novel therapeutic strategies that offer potent anti-tumor activity with minimal toxicity are urgently needed to combat the threat of breast cancer and lung metastases. Celastrol (Cela), a triterpenoid extracted from Tripterygium wilfordii, exerts anti-tumor effects by inhibiting tumor angiogenesis as well as tumor cell proliferation, invasion, and metastasis. However, its poor solubility and potential for severe organ toxicity hinder its clinical application. Therefore, in this study, we prepared Cela nanocrystals (Cela-NCs), which effectively increased the solubility of Cela and improved its bioavailability. Subsequently, Cela-NCs were encapsulated within the cell membrane (CCM) derived from breast cancer cells to generate CCM/Cela-NCs and leverage the homologous targeting ability of the CCM. Notably, CCM/Cela-NCs showed immune evasion and could homologously target tumor cells. Both in vitro and in vivo, CCM/Cela-NCs could effectively inhibit the growth and metastasis of breast cancer cells. They also exerted minimal hepatotoxicity in mice during treatment. In conclusion, this Cela-based biomimetic strategy that exploits the biological properties of tumor cells offers a new idea for the effective treatment of breast cancer and its lung metastasis.