CENAB, Faculty of Science, Jan Evangelista Purkyně University in Ústí Nad Labem, Ústí nad Labem, Czech Republic.
Institute of Chemical Process Fundamentals of the CAS, Prague, Czech Republic.
Sci Rep. 2023 Sep 19;13(1):15477. doi: 10.1038/s41598-023-42850-3.
The consideration of human and environmental exposure to dendrimers, including cytotoxicity, acute toxicity, and cell and tissue accumulation, is essential due to their significant potential for various biomedical applications. This study aimed to evaluate the biodistribution and toxicity of a novel methoxyphenyl phosphonium carbosilane dendrimer, a potential mitochondria-targeting vector for cancer therapeutics, in 2D and 3D cancer cell cultures and zebrafish embryos. We assessed its cytotoxicity (via MTT, ATP, and Spheroid growth inhibition assays) and cellular biodistribution. The dendrimer cytotoxicity was higher in cancer cells, likely due to its specific targeting to the mitochondrial compartment. In vivo studies using zebrafish demonstrated dendrimer distribution within the vascular and gastrointestinal systems, indicating a biodistribution profile that may be beneficial for systemic therapeutic delivery strategies. The methoxyphenyl phosphonium carbosilane dendrimer shows promise for applications in cancer cell delivery, but additional studies are required to confirm these findings using alternative labelling methods and more physiologically relevant models. Our results contribute to the growing body of evidence supporting the potential of carbosilane dendrimers as vectors for cancer therapeutics.
由于树状大分子在各种生物医学应用中具有显著的潜力，因此考虑人类和环境对其的暴露，包括细胞毒性、急性毒性以及细胞和组织积累，是至关重要的。本研究旨在评估一种新型甲氧基苯膦基碳硅烷树状大分子的生物分布和毒性，该分子是一种潜在的用于癌症治疗的线粒体靶向载体，在 2D 和 3D 癌细胞培养物和斑马鱼胚胎中进行了评估。我们评估了其细胞毒性（通过 MTT、ATP 和球体生长抑制测定）和细胞内生物分布。该树状大分子在癌细胞中的细胞毒性更高，这可能是由于其对线粒体区室的特异性靶向。使用斑马鱼进行的体内研究表明，树状大分子在血管和胃肠道系统内分布，表明其生物分布特征可能有利于全身性治疗递送策略。甲氧基苯膦基碳硅烷树状大分子在癌症细胞递送上具有应用前景，但需要使用替代标记方法和更符合生理的模型进行更多研究，以证实这些发现。我们的研究结果为碳硅烷树状大分子作为癌症治疗载体的潜在应用提供了更多的证据支持。
