基于多功能介孔聚多巴胺的 STING 激动剂系统递送用于增强协同光热免疫治疗,Advanced Functional Materials

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基于多功能介孔聚多巴胺的 STING 激动剂系统递送用于增强协同光热免疫治疗
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-09-15 , DOI: 10.1002/adfm.202307241
Wenfeng Zeng ₁ , Zimu Li ₁ , Qili Huang ₁ , Chendi Ding ₂ , Li Yang ₁ , Wenyan Wang ₁ , Zhaoqing Shi ₂ , Yao Yang ₁ , Hongzhong Chen ₁ , Lin Mei _{2,

3} , Xiaowei Zeng ₁

Affiliation

STING激动剂在各种恶性肿瘤中的治疗应用受到无法全身给药和免疫抑制肿瘤微环境等因素的限制。在此，这项工作报告了一种基于介孔聚多巴胺的多功能纳米平台，负载有STING激动剂MSA-2并与Mn ²⁺螯合，用于协同光热和基于STING激活的免疫治疗。该纳米平台有效地将 MSA-2 递送至肿瘤部位，并在光热效应的促进下通过酸降解智能地释放其内容物。此外，肿瘤组织的热消融可以诱导免疫原性细胞死亡，这有助于缓解免疫抑制的肿瘤微环境，从而增强MSA-2的疗效。此外，Mn ²⁺作为双重作用的 STING 敏化剂和 MRI 造影剂，不仅可以增强免疫反应，还可以对纳米平台进行实时 MRI 跟踪。事实证明，该策略在阻止原发性/转移性肿瘤和引发强大的肿瘤特异性免疫反应方面都非常有效。总的来说，本文重点介绍了一种有效的多功能纳米平台，用于全身递送 STING 激动剂，协同光热疗法和 STING 通路激活介导的免疫疗法，为优化癌症治疗的联合疗法提供新的思路和策略。

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Multifunctional Mesoporous Polydopamine-Based Systematic Delivery of STING Agonist for Enhanced Synergistic Photothermal-Immunotherapy

The therapeutic application of STING agonists in various malignancies has been limited by factors such as the inability of systemic administration and the immunosuppressive tumor microenvironment. Herein, this work reports a mesoporous polydopamine-based multifunctional nanoplatform loaded with STING agonist MSA-2 and chelated with Mn²⁺ for synergistic photothermal and STING activation-based immunotherapy. The nanoplatform effectively delivers MSA-2 to the tumor site and intelligently releases its contents through acid degradation, facilitated by the photothermal effect. Additionally, the thermal ablation of tumor tissue can induce immunogenic cell death, which helps alleviate the immunosuppressive tumor microenvironment, thereby enhancing the efficacy of MSA-2. Furthermore, Mn²⁺ works as a dual-acting STING sensitizer and MRI contrast agent which not only boosts the immune response but also allows real-time MRI tracking of the nanoplatform. This strategy is proved highly efficacious both in impeding primary/metastatic tumor and in eliciting a robust tumor-specific immune response. Collectively, an effective multifunctional nanoplatform for the systemic delivery of STING agonist which synergized photothermal therapy and STING pathway activation-mediated immunotherapy is highlighted here to provide new ideas and strategies for optimizing combination therapy for cancer treatment.

更新日期：2023-09-15

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