Sharma Rakesh Kumar, Cwiklinski Katherine, Aalinkeel Ravikumar, Reynolds Jessica L, Sykes Donald E, Quaye Elizabeth, Oh James, Mahajan Supriya D, Schwartz Stanley A
a Department of Medicine Division of Allergy, Immunology, and Rheumatology, University at Buffalo , Clinical and Translational Research Center , NY , USA.
Immunol Invest. 2017 Nov;46(8):833-846. doi: 10.1080/08820139.2017.1371908.
We synthesized and characterized curcumin-stabilized silver nanoparticles (Cur-AgNP) and found them to be 45 nm by dynamic light scattering with a maximum absorbance at 406 nm. We evaluated Cur-AgNP for immunomodulatory activities and their potential as an antiretroviral agent. The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with human immunodeficiency virus (HIV)-1. ACH-2 cells, 200,000/ml, were treated with Cur-AgNP for 24-48 h. Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1β, TNF-α, and NF-κB was quantitated. Treatment of ACH-2 cells latently infected with HIV-1 with Cur-AgNP produced no toxic effects but significantly inhibited the expression of HIV-1 LTR (-73%, P < 0.01) and p24 (-57%, P < 0.05), IL-1βα (-61%, P < 0.01), TNF-αα (-54%, P < 0.05), IL-6 (-68%, P < 0.01), and NF-κB (-79%, P < 0.0001) as compared to untreated controls. Thus, Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as having immunomodulatory activities inhibiting the expression of pro-inflammatory mediators induced by infection with HIV-1. Experimental controls, such as curcumin alone, and conventional silver nanoparticles capped with citric acid, produced no similar biological effects. We conclude that treatment of HIV-1 infected cells with Cur-AgNP significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway.
我们合成并表征了姜黄素稳定的银纳米颗粒（Cur-AgNP），通过动态光散射发现其粒径为45 nm，最大吸光度在406 nm处。我们评估了Cur-AgNP的免疫调节活性及其作为抗逆转录病毒药物的潜力。在潜伏感染人类免疫缺陷病毒（HIV）-1的ACH-2细胞中测定了Cur-AgNP的抗逆转录病毒作用。将每毫升200,000个ACH-2细胞用Cur-AgNP处理24至48小时。对HIV-1 LTR和p24、促炎细胞因子IL-1β、TNF-α以及NF-κB的表达进行了定量分析。用Cur-AgNP处理潜伏感染HIV-1的ACH-2细胞未产生毒性作用，但与未处理的对照相比，显著抑制了HIV-1 LTR（-73%，P < 0.01）和p24（-57%，P < 0.05）、IL-1βα（-61%，P < 0.01）、TNF-αα（-54%，P < 0.05）、IL-6（-68%，P < 0.01）以及NF-κB（-79%，P < 0.0001）的表达。因此，Cur-AgNP作为直接抗逆转录病毒药物具有治疗潜力，同时具有免疫调节活性，可抑制HIV-1感染诱导的促炎介质的表达。实验对照，如单独的姜黄素以及用柠檬酸包覆的传统银纳米颗粒，未产生类似的生物学效应。我们得出结论，用Cur-AgNP处理HIV-1感染的细胞可通过抑制NF-κB核转位以及促炎细胞因子IL-1β、TNF-α和IL-6的下游表达，显著降低HIV的复制。随后使用HIV感染的人源化小鼠模型对Cur-AgNP进行体内研究正在进行中。
