Radiation-Activated Resiquimod Prodrug Nanomaterials for Enhancing Immune Checkpoint Inhibitor Therapy,Nano Letters

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Radiation-Activated Resiquimod Prodrug Nanomaterials for Enhancing Immune Checkpoint Inhibitor Therapy
Nano Letters ( IF 9.6 ) Pub Date : 2024-02-27 , DOI: 10.1021/acs.nanolett.4c00114
Jiali Sun _{1,

2} , Haochen Yao ₃ , Xitong Ren _{2,

4} , Linjie Cui _{2,

4} , Linlin Liu ₅ , Guoqing Wang ₁ , Zhaohui Tang _{2,

4}

Affiliation

Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5–30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult. Here, maleimide-modified resiquimod (R848) prodrug nanoparticles (MAL-NPs) are reported and combined with radiotherapy (RT) and anti-PD1 to enhance ICI therapy. MAL-NPs can promote antigen endocytosis by dendritic cells and are radio-reduced to produce R848. When combined with RT, MAL-NPs can augment the concentration of nanoparticles at tumor sites and be selectively radio-reduced within the tumor, thereby triggering a potent antitumor immune response. The systemic immune response and long-term memory efficacy induced by MAL-NPs + RT + anti-PD1 significantly inhibit the abscopal tumor growth and prevent tumor recurrence. This strategy can achieve systemic therapy through selective training of the tumor immune microenvironment, offering a new approach to overcome the obstacles of ICI therapy.

中文翻译：

辐射激活瑞西莫德前药纳米材料增强免疫检查点抑制剂治疗

免疫检查点抑制剂（ICI）疗法可有效用于治疗各种恶性肿瘤。然而，由于不同肿瘤的免疫反应存在差异，反应率被限制在 5-30%。用单一疗法克服多步免疫激活的所有障碍是很困难的。在此，报道了马来酰亚胺修饰的瑞西莫德 (R848) 前药纳米颗粒 (MAL-NP) 与放疗 (RT) 和抗 PD1 相结合以增强 ICI 治疗。 MAL-NPs 可以促进树突状细胞的抗原内吞作用，并被放射性还原产生 R848。当与 RT 结合时，MAL-NP 可以增加肿瘤部位纳米颗粒的浓度，并在肿瘤内选择性地进行放射还原，从而引发有效的抗肿瘤免疫反应。 MAL-NPs+RT+抗PD1诱导的全身免疫反应和长期记忆功效显着抑制远隔肿瘤生长并防止肿瘤复发。该策略可以通过选择性训练肿瘤免疫微环境实现全身治疗，为克服ICI治疗障碍提供了新途径。

更新日期：2024-02-27

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