Nanoconjugates to enhance PDT-mediated cancer immunotherapy by targeting the indoleamine-2,3-dioxygenase pathway.
Nanoconjugates to enhance PDT-mediated cancer immunotherapy by targeting the indoleamine-2,3-dioxygenase pathway.
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DOI：
10.1186/s12951-021-00919-z
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发表时间：
2021-06-14
影响因子：
10.2
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Yang X;Zhang W;Jiang W;Kumar A;Zhou S;Cao Z;Zhan S;Yang W;Liu R;Teng Y;Xie J
光动力疗法(PDT)除了能杀死癌细胞外，还能诱导抗肿瘤免疫反应。然而，光动力疗法作为一种单一疗法，往往不能诱导出强大的免疫力。免疫检查点抑制剂可以选择性地阻断调节轴，可以与PDT联合使用以改善治疗结果。吲哚胺2，3-双加氧酶(IDO)是一种免疫调节酶，是肿瘤免疫逃逸的重要调节因子。PDT和IDO靶向免疫检查点阻断的联合治疗很有前景，但很少被探索。在这里，我们报告了一种复合纳米颗粒，它允许同时传递光敏剂和IDO抑制剂。简单地说，我们将光敏剂ZnF16Pc和吲哚胺2，3-双加氧酶(IDO)抑制剂NLG919分别负载到铁蛋白和聚丙交酯-乙醇酸嵌段聚乙二醇纳米粒中，然后将这两个隔间连接起来，形成被称为PPF NPs的复合纳米粒子。我们首先在B16F10荷瘤C57/BL6小鼠体内测试了PPF纳米粒的联合治疗。我们的结果表明，PPF纳米粒子可以有效地包裹ZnF16Pc和NLG919。体内研究发现，联合治疗显著改善了肿瘤抑制和动物存活。此外，治疗还增加了CD8+ T细胞的肿瘤浸润，而降低了MDSCs和Treg细胞的频率。30%的动物肿瘤完全根除，它们成功地拒绝了第二次肿瘤接种。总体而言，我们的研究引入了一种独特的复合纳米平台，允许光敏剂和IDO抑制剂在最小的物种间干扰下共同传递，这是联合治疗的理想选择。网上版载有补充材料，可在10.1186/s12951-021-00919-z查阅。
Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored. Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF16Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice. Our results showed that PPF NPs can efficiently encapsulate both ZnF16Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8+ T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy. The online version contains supplementary material available at 10.1186/s12951-021-00919-z.
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影响因子：
8.8
作者：
Holmgaard RB;Zamarin D;Li Y;Gasmi B;Munn DH;Allison JP;Merghoub T;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
3.7
作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
10.8
作者：
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通讯作者：
Chen X
影响因子：
17.1
作者：
Xu, Jun;Xu, Ligeng;Liu, Zhuang
通讯作者：
Liu, Zhuang