PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function.
PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function.
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DOI：
10.1007/s12274-020-2684-1
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发表时间：
2020-03
期刊：
影响因子：
9.9
通讯作者：
Fernandes R
中科院分区：
文献类型：
--
作者：
Sweeney EE;Balakrishnan PB;Powell AB;Bowen A;Sarabia I;Burga RA;Jones RB;Bosque A;Cruz CRY;Fernandes R
自然杀伤（NK）细胞是天然免疫系统对抗人类免疫缺陷病毒（HIV）和癌症的有吸引力的效应细胞。然而，NK细胞疗法受到靶细胞逃避NK细胞的事实的限制，例如，在潜伏储库中（在HIV中）或通过上调抑制信号（在癌症中）。为了解决这一限制，我们描述了一种基于生物可降解纳米颗粒的“引发”方法，以增强外周血单核细胞衍生的NK细胞的细胞毒性功效。我们提出了聚（乳酸-羟基乙酸共聚物）（PLGA）纳米库（ND），共封装prostratin，一种潜伏期逆转剂，和抗CD 25（aCD 25），一种细胞表面结合抗体，以增强初级NK细胞对HIV和癌症的功能。我们利用纳米乳液合成方案将prostratin和aCD 25两者包封在PLGA ND（称为Pro-aCD 25-ND）内。ND的物理化学表征研究表明，我们的合成方案产生稳定且单分散的Pro-aCD 25-ND。NDs成功地释放了活性prostratin和抗CD 25，并且具有可控的释放动力学。当使用J-Lat 10.6细胞在潜伏HIV和急性T细胞白血病的体外模型中施用Pro-aCD 25-ND时，观察到ND引发J-Lat细胞，导致与游离prostratin加抗CD 25和其他对照相比显著增加的NK细胞介导的细胞毒性。这些发现证明了使用我们的Pro-aCD 25-ND来引发靶细胞以增强NK细胞作为抗病毒剂或抗肿瘤剂的细胞毒性的可行性。
Natural killer (NK) cells are attractive effector cells of the innate immune system against human immunodeficiency virus (HIV) and cancer. However, NK cell therapies are limited by the fact that target cells evade NK cells, for example, in latent reservoirs (in HIV) or through upregulation of inhibitory signals (in cancer). To address this limitation, we describe a biodegradable nanoparticle-based “priming” approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells. We present poly(lactic-co-glycolic acid) (PLGA) nanodepots (NDs) that co-encapsulate prostratin, a latency-reversing agent, and anti-CD25 (aCD25), a cell surface binding antibody, to enhance primary NK cell function against HIV and cancer. We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs (termed Pro-aCD25-NDs). Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs. The NDs successfully released both active prostratin and anti-CD25, and with controllable release kinetics. When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells, the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25, and other controls. These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.
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影响因子：
5.6
作者：
Gdowski A;Ranjan A;Mukerjee A;Vishwanatha J
通讯作者：
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影响因子：
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作者：
Chen, Mingshui;Ouyang, Haichao;Ye, Yunbin
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Ye, Yunbin
DOI：
10.1016/s0939-6411(03)00104-8
发表时间：
2003-09-01
影响因子：
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影响因子：
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通讯作者：
Verdin, E