Du Shuang, Wu Kemeng, Guan Yucheng, Lin Xiangping, Gao Sijia, Huang Shuiqing, Shi Xuguang, Wang Lisheng, Chen Xiaojia, Chen Tongkai
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078 China.
Int J Pharm. 2025 Feb 25;671:125221. doi: 10.1016/j.ijpharm.2025.125221. Epub 2025 Jan 19.
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.
乳腺癌及其肺转移对全球女性健康构成重大威胁，影响她们的生活质量。尽管已经开发了几种针对乳腺癌的治疗策略，但由于其高毒性和低特异性，它们常常会引起严重的副作用。因此，迫切需要新的治疗策略，既能提供强大的抗肿瘤活性，又能将毒性降至最低，以对抗乳腺癌和肺转移的威胁。雷公藤红素（Celastrol，Cela）是从雷公藤中提取的一种三萜类化合物，通过抑制肿瘤血管生成以及肿瘤细胞的增殖、侵袭和转移发挥抗肿瘤作用。然而，其溶解度差和潜在的严重器官毒性阻碍了它的临床应用。因此，在本研究中，我们制备了雷公藤红素纳米晶体（Cela-NCs），它有效地提高了雷公藤红素的溶解度并改善了其生物利用度。随后，将Cela-NCs包裹在源自乳腺癌细胞的细胞膜（CCM）中，生成CCM/Cela-NCs，并利用CCM的同源靶向能力。值得注意的是，CCM/Cela-NCs表现出免疫逃逸能力，并且能够同源靶向肿瘤细胞。在体外和体内，CCM/Cela-NCs都能有效抑制乳腺癌细胞的生长和转移。在治疗过程中，它们对小鼠的肝毒性也最小。总之，这种基于雷公藤红素的仿生策略利用了肿瘤细胞的生物学特性，为有效治疗乳腺癌及其肺转移提供了新思路。
