Inhibition of Influenza A Virus Infection in Vitro by Saliphenylhalamide-Loaded Porous Silicon Nanoparticles
Inhibition of Influenza A Virus Infection in Vitro by Saliphenylhalamide-Loaded Porous Silicon Nanoparticles
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DOI：
10.1021/nn402062f
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发表时间：
2013-08-01
期刊：
影响因子：
17.1
通讯作者：
Santos, Helder A.
中科院分区：
文献类型：
--
作者：
Bimbo, Luis M.;Denisova, Oxana V.;Santos, Helder A.
甲型流感病毒 (IAV) 在人类中引起反复流行，严重威胁全球范围内致命的流行病。抗病毒耐药病毒株的出现和高致病性流感病毒的出现引发了开发新的抗IAV治疗方法的迫切需要。水利苯卤酰胺 (SaliPhe) 是一种被发现可以抑制 IAV 和其他病毒感染的化合物。 SaliPhe 靶向宿主液泡 ATP 酶并抑制内体酸化，这是有效病毒感染所需的过程。 SaliPhe作为抗病毒药物进一步开发的主要障碍是其溶解度差。在这里，我们研究了通过将化合物负载到热烃化多孔硅 (THCPSi) 纳米颗粒中来增加 SaliPhe 溶解度的可能性。进一步研究了负载 SaliPhe 的纳米颗粒抑制人视网膜色素上皮和 Madin-Darby 犬肾细胞中甲型流感病毒感染的能力，我们发现，从 THCPSI 中释放后，SaliPhe 在体外抑制了 IAV 感染，并减少了 IAV 感染细胞中子代病毒的数量。总体而言，基于 PSi 的纳米系统表现出所研究的抗 IAV 药物 SaliPhe 的溶出度增加，并表现出优异的体外稳定性、低细胞毒性，并且在没有有机溶剂的情况下显着降低病毒载量：这项原理验证研究表明 PSi 纳米颗粒可用于将抗病毒药物有效递送至受感染的细胞。
Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSI, SaliPhe inhibited IAV Infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents:This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.