Background: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.
Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.
Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.
Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.
Graphical Abstract:



中文翻译：

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具有白蛋白稳定和负载石墨烯的镓金属有机纳米颗粒，用于增强对 HCT116 细胞的递送

背景：镓 (III) 金属有机络合物已被证明具有抑制肿瘤生长的能力，但许多络合物的水溶性差阻碍了进一步的应用。使用具有高生物相容性的材料作为金属有机配合物的药物递送载体，提高药物的生物利用度是一种可行的途径。
方法：在这里，我们通过用 5-bromo-8-hydroxyquinoline (HBrQ) 替换 8-hydroxyquinoline 配体来修饰具有良好临床抗癌活性的 8-hydroxyquinolinate 镓络合物的配体，并且所得 Ga(III) + HBrQ 络合物具有较差的水溶性. 两种生物相容性材料，牛血清白蛋白 (BSA) 和氧化石墨烯 (GO)，以不同方式合成相应的 Ga(III) + HBrQ 复合纳米粒子 (NPs) BSA/Ga/HBrQ NPs 和 GO/Ga/HBrQ NPs以增强金属络合物的药物递送。
结果：BSA/Ga/HBrQ NPs和GO/Ga/HBrQ NPs都可以在不同的溶液状态下保持稳定存在。体外细胞毒性试验表明，两种纳米药物对HCT116细胞具有优异的抗增殖作用，细胞内ROS水平和凋亡率均高于顺铂和奥沙利铂。此外，BSA/Ga/HBrQ NPs 和 GO/Ga/HBrQ NPs 的优异发射特性允许它们用于体内成像，显示出在 HCT116 荷瘤小鼠模型中的高效治疗。
结论：使用生物相容性材料制备 NPs 以对抗生物相容性差的金属有机络合物来构建药物递送系统是一种有前途的策略，可以进一步提高药物递送和治疗效果。
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