Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy.,Nano Letters

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Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy.
Nano Letters ( IF 9.6 ) Pub Date : 2020-06-17 , DOI: 10.1021/acs.nanolett.0c00893
Jing Liu _{1,

2} , Hong-Jun Li ₃ , Ying-Li Luo ₃ , Yi-Fang Chen ₃ , Ya-Nan Fan ₁ , Jin-Zhi Du ₃ , Jun Wang _{1,

4,

5,

6}

Affiliation

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.

中文翻译：

免疫佐剂的可编程递送至肿瘤浸润的树突状细胞，用于癌症免疫治疗。

肿瘤浸润性树突状细胞（TIDC）大多不成熟且具有免疫抑制作用，通常介导免疫抑制作用。已证明利用胞嘧啶-鸟嘌呤寡脱氧核苷酸（CpG ODN）刺激TIDC的激活可有效提高抗肿瘤免疫力。但是，一系列的生物屏障限制了先前的纳米载体将CpG传递到TIDC的功效。在这里，我们开发了一种基于双敏树枝状聚合物簇的纳米佐剂，用于将CpG ODN传递到TIDC中。我们显示，肿瘤的酸度触发了CpG共轭聚酰胺酰胺（PAMAM）树状大分子从纳米佐剂中的快速释放，从而促进了其向TIDCs的深层灌注和吞噬作用。此后，溶酶体的还原状态导致CpG的后续释放，促进DCs活化并增强抗肿瘤免疫疗法。免疫佐剂的可编程递送有效地克服了靶向递送至TIDC的障碍，并为改善癌症免疫疗法提供了有希望的策略。

更新日期：2020-07-08

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