Institute of Inorganic Chemistry, Karlsruhe Institute of Technology (KIT), Engesserstrasse 15, D-76131 Karlsruhe, Germany.
Helmholtz Center for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
ACS Biomater Sci Eng. 2022 Apr 11;8(4):1596-1603. doi: 10.1021/acsbiomaterials.2c00074. Epub 2022 Mar 28.
[ZrO][(FCN)(OH)] and Gd[FCN] inorganic-organic hybrid nanoparticles (IOH-NPs) are novel saline antiviral nanocarriers with foscarnet (FCN) as a drug anion. FCN as a pyrophosphate analogue serves as a prototype of a viral DNA polymerase inhibitor. FCN is used for the treatment of herpesvirus infections, including the drug-resistant cytomegalovirus (CMV) and herpes simplex viruses, HSV-1 and HSV-2. The novel [ZrO][(FCN)(OH)] and Gd[FCN] IOH-NPs are characterized by aqueous synthesis, small size (20-30 nm), low material complexity, high biocompatibility, and high drug load (up to 44 wt % FCN per nanoparticle). The antiviral activity of the FCN-type IOH-NPs is probed for the human cytomegalovirus (HCMV). Moreover, the uptake of FCN-type IOH-NPs into vesicles, cytoplasm, and nuclei of nonphagocytic lung epithelial cells is evaluated. As a result, a promising antiviral activity of the FCN-type IOH-NPs that significantly outperforms freely dissolved FCN at the level of clinical formulations is observed, encouraging a future use of FCN-type IOH-NPs for the delivery of antivirals against respiratory viruses.
[ZrO][(FCN)(OH)]和 Gd[FCN]无机-有机杂化纳米粒子（IOH-NPs）是新型的盐性抗病毒纳米载体，其药物阴离子为膦甲酸（FCN）。作为焦磷酸盐类似物，FCN 可用作病毒 DNA 聚合酶抑制剂的原型。FCN 用于治疗疱疹病毒感染，包括耐药性巨细胞病毒（CMV）和单纯疱疹病毒 1 型和 2 型。新型[ZrO][(FCN)(OH)]和 Gd[FCN] IOH-NPs 的特点是水相合成、粒径小（20-30nm）、材料复杂度低、生物相容性高、药物载量高（每个纳米颗粒高达 44wt%FCN）。研究了 FCN 型 IOH-NPs 对人巨细胞病毒（HCMV）的抗病毒活性。此外，还评估了 FCN 型 IOH-NPs 进入非吞噬性肺上皮细胞的囊泡、细胞质和细胞核的摄取情况。结果表明，与游离 FCN 相比，FCN 型 IOH-NPs 具有显著的抗病毒活性，明显优于临床制剂水平，这为 FCN 型 IOH-NPs 用于呼吸道病毒抗病毒药物的递送提供了未来应用的可能。
