Heidari-Kharaji Maryam, Rodrigues Priscilla, Ferreira Christina, Pooneiad Robinson Pavene, Sajid Sadia
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Parasite Immunol. 2025 Jul;47(7):e70017. doi: 10.1111/pim.70017.
The interest in nanotechnology applications in medicine, particularly for combating microbial infections, has surged in recent years. This study investigated the in vitro and in vivo antileishmanial effects of copper nanoparticles (CuNPs) that were green synthesised using Capparis spinosa fruit extract, both on their own and in conjunction with paromomycin (PM). CuNPs were synthesised from a methanolic extract of C. spinosa. We assessed the in vitro antileishmanial activity of CuNPs (10-200 μg/mL) as well as the same concentrations of CuNPs (10-200 μg/mL) combined with PM (10-200 μg/mL), targeting the promastigote and amastigote forms of Leishmania major. Additionally, we evaluated the cytotoxic effects of CuNPs on THP1 cells. Subsequently, we tested these formulations on female BALB/c mice infected with L. major. The study measured footpad swelling, quantified parasite load through real-time PCR, and assessed levels of cytokines such as interleukin-4 (IL-4) and gamma interferon (IFN-ɤ), nitric oxide (NO), and arginase (ARG). The results demonstrated that CuNPs, particularly when combined with PM, significantly inhibited (p < 0.001) the growth of L. major promastigotes and amastigotes and stimulated IFN-ɤ, NO production and reduced IL-4 and ARG levels (p < 0.05). Importantly, CuNPs exhibited minimal cytotoxicity towards THP1 cells. In infected mice, the treatment with CuNPs, notably in combination with PM, resulted in a significant (p < 0.05) reduction in the mean number of parasites. Treatment with CuNPs at concentrations of 100 and 200 mg/mL led to a decrease in lesion diameter. The results of this study highlight the potent antileishmanial activity and synergistic effects of CuNPs, both alone and in combination with PM, against L. major promastigotes and amastigote forms, as well as their potential in treating cutaneous leishmaniasis (CL) in BALB/c mice.
近年来，纳米技术在医学领域的应用，尤其是在对抗微生物感染方面的应用兴趣激增。本研究调查了使用刺山柑果实提取物绿色合成的铜纳米颗粒（CuNPs）单独及与巴龙霉素（PM）联合使用时的体外和体内抗利什曼原虫作用。CuNPs由刺山柑的甲醇提取物合成。我们评估了CuNPs（10 - 200μg/mL）以及相同浓度的CuNPs（10 - 200μg/mL）与PM（10 - 200μg/mL）联合使用时针对硕大利什曼原虫前鞭毛体和无鞭毛体形式的体外抗利什曼原虫活性。此外，我们评估了CuNPs对THP1细胞的细胞毒性作用。随后，我们在感染硕大利什曼原虫的雌性BALB/c小鼠身上测试了这些制剂。该研究测量了足垫肿胀情况，通过实时PCR定量寄生虫载量，并评估了白细胞介素 - 4（IL - 4）、γ干扰素（IFN -ɤ）、一氧化氮（NO）和精氨酸酶（ARG）等细胞因子的水平。结果表明，CuNPs，特别是与PM联合使用时，显著抑制（p < 0.001）硕大利什曼原虫前鞭毛体和无鞭毛体的生长，并刺激IFN -ɤ、NO的产生，降低IL - 4和ARG水平（p < 0.05）。重要的是，CuNPs对THP1细胞表现出最小的细胞毒性。在感染小鼠中，用CuNPs治疗，特别是与PM联合使用时，导致寄生虫平均数量显著减少（p < 0.05）。用浓度为100和200mg/mL的CuNPs治疗导致病变直径减小。本研究结果突出了CuNPs单独及与PM联合使用时对硕大利什曼原虫前鞭毛体和无鞭毛体形式的强效抗利什曼原虫活性和协同作用，以及它们在治疗BALB/c小鼠皮肤利什曼病（CL）方面的潜力。
