Klein Stefanie, Luchs Tobias, Leng Andreas, Distel Luitpold V R, Neuhuber Winfried, Hirsch Andreas
Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen Nuremberg, Egerlandstr. 3, D-91058 Erlangen, Germany.
Department of Chemistry and Pharmacy, Chair of Organic Chemistry II, Friedrich-Alexander University of Erlangen Nuremberg, Nikolaus-Fiebiger-Str. 10, D-91058 Erlangen, Germany.
Bioengineering (Basel). 2020 Oct 12;7(4):126. doi: 10.3390/bioengineering7040126.
Our research objective was to develop novel drug delivery vehicles consisting of TiO and AlO nanoparticles encapsulated by a bilayer shell that allows the reversible embedment of hydrophobic drugs. The first shell is formed by covalent binding of hydrophobic phosphonic acid at the metal oxide surface. The second shell composed of amphiphilic sodium dodecylbenzenesulfonate emerges by self-aggregation driven by hydrophobic interactions between the dodecylbenzene moiety and the hydrophobic first shell. The resulting double layer provides hydrophobic pockets suited for the intake of hydrophobic drugs. The nanoparticles were loaded with the anticancer drugs quercetin and 7-amino-4-methylcoumarin. Irradiation with X-rays was observed to release the potential anticancer drugs into the cytoplasm. In Michigan Cancer Foundation (MCF)-10 A cells, quercetin and 7-amino-4-methylcoumarin acted as antioxidants by protecting the non-tumorigenic cells from harmful radiation effects. In contrast, these agents increased the reactive oxygen species (ROS) formation in cancerous MCF-7 cells. Quercetin and 7-amino-4-methylcoumarin were shown to induce apoptosis via the mitochondrial pathway in cancer cells by determining an increase in TUNEL-positive cells and a decrease in mitochondrial membrane potential after irradiation. After X-ray irradiation, the survival fraction of MCF-7 cells with drug-loaded nanoparticles considerably decreased, which demonstrates the excellent performance of the double-layer stabilized nanoparticles as drug delivery vehicles.
我们的研究目标是开发新型药物递送载体，该载体由包裹在双层壳中的二氧化钛和氧化铝纳米颗粒组成，双层壳允许疏水性药物可逆嵌入。第一层壳是通过疏水性膦酸在金属氧化物表面的共价结合形成的。由两亲性十二烷基苯磺酸钠组成的第二层壳通过十二烷基苯部分与疏水性第一层壳之间的疏水相互作用驱动的自聚集而出现。形成的双层提供了适合摄入疏水性药物的疏水口袋。纳米颗粒装载了抗癌药物槲皮素和7-氨基-4-甲基香豆素。观察到用X射线照射可将潜在的抗癌药物释放到细胞质中。在密歇根癌症基金会（MCF）-10 A细胞中，槲皮素和7-氨基-4-甲基香豆素通过保护非致瘤细胞免受有害辐射影响而起到抗氧化剂的作用。相反，这些药物增加了癌细胞系MCF-7细胞中活性氧（ROS）的形成。槲皮素和7-氨基-4-甲基香豆素通过测定照射后TUNEL阳性细胞的增加和线粒体膜电位的降低，显示出通过线粒体途径诱导癌细胞凋亡。X射线照射后，载有药物的纳米颗粒处理的MCF-7细胞的存活分数显著降低，这证明了双层稳定纳米颗粒作为药物递送载体的优异性能。
