Wedler Vincent, Stiegler Lisa M S, Gandziarowski Teresa, Walter Johannes, Peukert Wolfgang, Distel Luitpold V R, Hirsch Andreas, Klein Stefanie
Department of Chemistry and Pharmacy, Chair of Organic Chemistry II, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, Erlangen D-91058, Germany.
Institute of Particle Technology (LFG), Friedrich-Alexander-Universität Erlangen-Nürnberg, Cauerstr. 4, Erlangen 91058, Germany; Interdisciplinary Center for Functional Particle Systems (FPS), Friedrich-Alexander-Universität Erlangen-Nürnberg, Haberstrasse 9a, Erlangen 91058, Germany.
Colloids Surf B Biointerfaces. 2025 Jan;245:114276. doi: 10.1016/j.colsurfb.2024.114276. Epub 2024 Sep 27.
Shell-by-Shell (SbS)-functionalized NPs can be tailor-made by combining a metal oxide NP core of choice with any desired phosphonic acids and amphiphiles as 1st or 2nd ligand shell building blocks. The complementary composition of such highly hierarchical structures makes them interesting candidates for various biomedical applications, as certain active ingredients can be incorporated into the structure. Here, we used TiO and CoFeO NPs as drug delivery tools and coated them with a hexadecylphosphonic acid and with hexadecyl ammonium phenolates (caffeate, p-coumarate, ferulate), that possess anticancer as well as antioxidant properties. These architectures were then incubated in 2D and 3D cell cultures of non-tumorigenic and tumorigenic breast cells and irradiated to study their anticancer effect. It was found that both, the functionalized TiO and CoFeO NPs acted as strong protective agents in non-tumorigenic spheroids. In contrast, the functionalized CoFeO NPs induce a higher damage in irradiated tumor spheroids compared to the functionalized TiO NPs. CoFeO NPs act additionally as radiosensitizing agents to the tumor spheroids. The radio-enhancement of the CoFeO NPs is due to the generation of highly toxic hydroxyl radicals during X-ray irradiation. The irradiation exposed the CoFeO surface, releasing the anticancer drugs into the cytoplasm and making the surface Co ions accessible. These surface ions catalyze the Fenton reaction. This combination of radiosensitizer and anticancer drug delivery proved to be a very effective nanotherapeutic in 2D and 3D cell cultures of breast cancer cells.
通过将选定的金属氧化物纳米颗粒核心与任何所需的膦酸和两亲物作为第一或第二配体壳构建块相结合，可以定制逐壳（SbS）功能化的纳米颗粒。这种高度分级结构的互补组成使其成为各种生物医学应用的有趣候选物，因为某些活性成分可以纳入该结构中。在这里，我们使用TiO和CoFeO纳米颗粒作为药物递送工具，并用具有抗癌和抗氧化特性的十六烷基膦酸和十六烷基苯酚盐（咖啡酸盐、对香豆酸盐、阿魏酸盐）对其进行包覆。然后将这些结构在非致瘤性和致瘤性乳腺癌细胞的二维和三维细胞培养物中孵育并进行辐照，以研究它们的抗癌效果。结果发现，功能化的TiO和CoFeO纳米颗粒在非致瘤性球体中均作为强保护剂。相比之下，与功能化的TiO纳米颗粒相比，功能化的CoFeO纳米颗粒在辐照后的肿瘤球体中诱导更高的损伤。CoFeO纳米颗粒还作为肿瘤球体的放射增敏剂。CoFeO纳米颗粒的放射增强作用是由于在X射线照射期间产生了剧毒的羟基自由基。辐照使CoFeO表面暴露，将抗癌药物释放到细胞质中并使表面的Co离子可及。这些表面离子催化芬顿反应。在乳腺癌细胞的二维和三维细胞培养中，这种放射增敏剂和抗癌药物递送的组合被证明是一种非常有效的纳米治疗方法。
