College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.
College of Life Science, Liaoning University, Shenyang 110036, People's Republic of China.
Nanotechnology. 2022 Aug 1;33(43). doi: 10.1088/1361-6528/ac197b.
Abnormal apoptosis can lead to uncontrolled cell growth, aberrant homeostasis or the accumulation of mutations. Therapeutic agents that re-establish the normal functions of apoptotic signaling pathways offer an attractive strategy for the treatment of breast cancer. Baicalin (BA) is one of the natural compounds with anti-proliferation and pro-apoptosis activities against numerous tumor cells. However, low bioavailability restricts the clinical application of BA. In order to improve its therapeutic efficacy and study the mechanism of actions, active targeting delivery systems were developed for targeting tumor environment and selective cell killing effects. It emphasized on the construction of folate-conjugated albumin nanoparticles loaded with baicalin (FA-BSANPs/BA) and mechanisms of which on the promotion of breast cancer apoptosis. The physicochemical properties and structural characteristics of FA-BSANPs/BA were investigated. Cell experiments were carried out to study the targeted anti-breast cancer effects of FA-BSANPs/BA and its mechanism. The results showed that FA-BSANPs/BA was successfully constructed with stable structural characteristics and sustained release effects. Cellular uptake and MTT showed that it increased targeted uptake efficiency and cytotoxicity. Flow cytometry and western blot confirmed that it promoted apoptosis by increasing the expression of caspase-8 and ROS, and decreasing the level of Bid. It is suggested that the pro-apoptotic mechanism of FA-BSANPs/BA is related to regulation of key proteins in extrinsic apoptotic pathway. In conclusion, FA-BSANPs/BA is a good delivery carrier and significantly inhibits the breast cancer growth compared with free BA. The mechanism of FA-BSANPs/BA promoting apoptosis of breast cancer may be due to its action on the caspase-8/Bid/ROS pathway.
异常凋亡可导致细胞失控生长、异常的体内平衡或突变的积累。重新建立凋亡信号通路正常功能的治疗药物为乳腺癌的治疗提供了一种有吸引力的策略。黄芩苷（BA）是对许多肿瘤细胞具有抗增殖和促凋亡作用的天然化合物之一。然而，其低生物利用度限制了 BA 的临床应用。为了提高其治疗效果并研究作用机制，开发了主动靶向递药系统，以针对肿瘤环境和选择性细胞杀伤作用。本文强调构建叶酸偶联白蛋白纳米粒载黄芩苷（FA-BSANPs/BA），并研究其促进乳腺癌细胞凋亡的作用机制。考察了 FA-BSANPs/BA 的理化性质和结构特征。进行细胞实验以研究 FA-BSANPs/BA 的靶向抗乳腺癌作用及其机制。结果表明，成功构建了具有稳定结构特征和持续释放效果的 FA-BSANPs/BA。细胞摄取和 MTT 表明，它增加了靶向摄取效率和细胞毒性。流式细胞术和 Western blot 证实，它通过增加 caspase-8 和 ROS 的表达，降低 Bid 的水平，促进细胞凋亡。提示 FA-BSANPs/BA 的促凋亡机制与调节外源性凋亡途径中的关键蛋白有关。总之，FA-BSANPs/BA 是一种良好的递药载体，与游离 BA 相比，能显著抑制乳腺癌的生长。FA-BSANPs/BA 促进乳腺癌细胞凋亡的机制可能与其作用于 caspase-8/Bid/ROS 通路有关。
