The emergence of drug-resistant pathogens causes the greatest challenge for drug development research. Recently, gallium(III)-based compounds have received great attention as novel antimicrobial agents against drug-resistant pathogens. Here, we synthesized a new β-cyclodextrin Ga nanoparticle (CDGaTP) using Ga tetraphenylporphyrin (GaTP, a hemin analogue) and β-cyclodextrin. The newly synthesized nanoparticle was nontoxic and efficient at a single dose, showing sustained drug release for 15 days in vitro. CDGaTP’s activity with transferrin or lactoferrin was tested, and synergism in activity was observed against nontuberculosis mycobacteria (NTM), Mycobacterium avium (M. avium), and Mycobacteroides abscessus. Human serum albumin (HSA) decreased the efficacy of both GaTP and CDGaTP in a concentration-dependent manner. The NTMs incubated with GaTP or CDGaTP significantly produced reactive oxygen species (ROS), indicating potential inhibition of antioxidant enzymes, such as catalase. The single-dose CDGaTP displayed a prolonged intracellular inhibitory activity in an in vitro macrophage infection model against both NTMs. In addition, CDGaTP, not GaTP, was effective in a murine lung M. avium infection model when delivered via intranasal administration. These results suggest that CDGaTP provides new opportunities for the development of gallium-porphyrin based antibiotics.

中文翻译：

---

含有四苯基卟啉镓的纳米颗粒 β-环糊精在体外和体内均显示出对脓肿分枝杆菌和鸟分枝杆菌的抗菌功效

耐药病原体的出现给药物开发研究带来了最大的挑战。最近，基于镓（III）的化合物作为针对耐药病原体的新型抗菌剂受到了极大的关注。在这里，我们使用Ga四苯基卟啉（GaTP，一种血红素类似物）和β-环糊精合成了一种新的β-环糊精Ga纳米颗粒（CDGaTP）。新合成的纳米颗粒在单次剂量下无毒且有效，在体外可持续释放药物 15 天。测试了 CDGaTP 与转铁蛋白或乳铁蛋白的活性，并观察到对非结核分枝杆菌 (NTM)、鸟分枝杆菌( M. avium ) 和分枝杆菌脓肿的协同作用. 人血清白蛋白 (HSA) 以浓度依赖性方式降低 GaTP 和 CDGaTP 的功效。与 GaTP 或 CDGaTP 孵育的 NTM 显着产生活性氧 (ROS)，表明可能抑制抗氧化酶，如过氧化氢酶。单剂量 CDGaTP 在体外巨噬细胞感染模型中对两种 NTM 显示出延长的细胞内抑制活性。此外，当通过鼻内给药递送时，CDGaTP，而非 GaTP，在鼠肺M.avium感染模型中是有效的。这些结果表明 CDGaTP 为开发基于镓卟啉的抗生素提供了新的机会。