Lai Yingmei, Zhang Zhongao, Yu Xintian, Cheng Zhuohang, Wu Songrui, Ding Jianzu, Huang Wenkang, Lu Shaohong, Ye Huayue, Ding Haojie, Zhuo Xunhui
School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical college, Hangzhou 310013, PR China.
School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical college, Hangzhou 310013, PR China.
Acta Trop. 2025 Sep;269:107740. doi: 10.1016/j.actatropica.2025.107740. Epub 2025 Jul 12.
Toxoplasma gondii (T. gondii), a globally prevalent zoonotic parasite, infects nucleated cells in warm-blooded animals, posing major public health risks. Current treatments (sulfadiazine/pyrimethamine) for the widespread parasite T. gondii have poor cyst penetration and significant side effects. While the natural compound baicalein (BAI, C₁₅H₁₀O₅) shows potent anti-T. gondii activity, its low solubility and high toxicity limit therapeutic use. To overcome BAI's limitations, we engineered ginsenoside Rb1-based nanoparticles (GRb1/BAI NPs) via self-assembly, leveraging GRb1's dual role as a biocompatible carrier and therapeutic booster. The GRb1/BAI NPs exhibited favorable characteristics, including ease of preparation, optimal particle size (∼110 nm), stable zeta potential (-33.82 ± 0.85 mV), high encapsulation efficiency (94.67 %) and drug load (36.09 %), and smooth sustained-release properties. In vitro and in vivo assessments revealed that the GRb1/BAI NPs exhibited limited cytotoxicity within the tested concentration range. Furthermore, compared with 70.28 μM of free BAI, the reduced IC value (41.53 μM) of GRb1/BAI NPs demonstrated enhanced drug potency and safety along with significant inhibition of intracellular T. gondii proliferation as determined by quantifying parasite burdens based on the 529 repetitive sequence (rep-529) gene standard curve. In vivo experiments further confirmed that GRb1/BAI NPs elicited more durable and protective effects against acute (RH strain) and chronic (PRU strain) toxoplasmosis with significantly prolonged survival time and notably reduced cysts numbers in mice brains. GRb1/BAI NPs show promise as novel anti-T. gondii agents by leveraging the carrier's therapeutic activity while using natural excipients, thereby avoiding toxicity risks from synthetic alternatives.
刚地弓形虫是一种全球流行的人畜共患寄生虫，可感染温血动物的有核细胞，对公众健康构成重大风险。目前用于治疗广泛存在的刚地弓形虫的药物（磺胺嘧啶/乙胺嘧啶）对包囊的穿透性较差，且有明显的副作用。虽然天然化合物黄芩素（BAI，C₁₅H₁₀O₅）显示出强大的抗刚地弓形虫活性，但其低溶解度和高毒性限制了其治疗用途。为了克服黄芩素的局限性，我们通过自组装工程化了基于人参皂苷Rb1的纳米颗粒（GRb1/BAI NPs），利用Rb1作为生物相容性载体和治疗增强剂的双重作用。GRb1/BAI NPs表现出良好的特性，包括易于制备、最佳粒径（约110nm）、稳定的zeta电位（-33.82±0.85mV）、高包封率（94.67%）和载药量（36.09%）以及良好的缓释性能。体外和体内评估表明，GRb1/BAI NPs在测试浓度范围内表现出有限的细胞毒性。此外，与70.28μM的游离黄芩素相比，GRb1/BAI NPs降低的IC值（41.53μM）表明其药物效力和安全性增强，同时通过基于529重复序列（rep-529）基因标准曲线定量寄生虫负荷确定，对细胞内刚地弓形虫增殖有显著抑制作用。体内实验进一步证实，GRb1/BAI NPs对急性（RH株）和慢性（PRU株）弓形虫病具有更持久的保护作用，可显著延长小鼠存活时间，并显著减少小鼠脑中的包囊数量。GRb1/BAI NPs通过利用载体的治疗活性，同时使用天然辅料，有望成为新型抗刚地弓形虫药物，从而避免合成替代品带来的毒性风险。
