Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Shandong Academy of Chinese Medicine, Jinan 250000, PR China.
Int J Pharm. 2022 Jun 25;622:121810. doi: 10.1016/j.ijpharm.2022.121810. Epub 2022 May 14.
In previous studies, we found that triphenylphosphine-modified doxorubicin (TPP-DOX) can effectively kill drug-resistant tumor cells, but its effect on sensitive tumor cells is weakened. In this research, with albumin from Bovine Serum (BSA) as a carrier, TPP-DOX@MnBSA (TD@MB) nanoparticles were prepared by co-loading TPP-DOX and manganese which can realize the combination of chemotherapy and chemodynamic therapy (CDT). The uniform and stable nano-spherical nanoparticle can promote drug uptake, achieve mitochondrial-targeted drug delivery, increase intracellular reactive oxygen species (ROS) and catalyze the production of highly toxic oxidative hydroxyl radicals (OH·), further inhibiting the growth of both sensitive and drug-resistant MCF-7 cells. Besides, TD@MB can down-regulate the stemness-related proteins and the metastasis-related proteins, potentially decreasing the tumor stemness and metastasis. In vivo experiment indicated that TD@MB was able to exert desired antitumor effect, good tumor targeting and biocompatibility.
在之前的研究中，我们发现三苯基膦修饰的阿霉素（TPP-DOX）可以有效地杀死耐药肿瘤细胞，但对敏感肿瘤细胞的作用减弱。在这项研究中，以牛血清白蛋白（BSA）为载体，通过共载三苯基膦修饰的阿霉素（TPP-DOX）和锰制备了 TPP-DOX@MnBSA（TD@MB）纳米粒子，实现了化疗和化学动力学治疗（CDT）的联合。均匀稳定的纳米球形纳米粒子可以促进药物摄取，实现线粒体靶向药物传递，增加细胞内活性氧（ROS）并催化产生高毒性的羟基自由基（OH·），进一步抑制敏感和耐药 MCF-7 细胞的生长。此外，TD@MB 可以下调干性相关蛋白和转移相关蛋白，可能降低肿瘤干性和转移。体内实验表明，TD@MB 能够发挥理想的抗肿瘤作用、良好的肿瘤靶向性和生物相容性。
