Urease-powered nanomotor containing STING agonist for bladder cancer immunotherapy.

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-11-15 DOI:10.1038/s41467-024-54293-z

Hyunsik Choi, Seung-Hwan Jeong, Cristina Simó, Anna Bakenecker, Jordi Liop, Hye Sun Lee, Tae Yeon Kim, Cheol Kwak, Gou Young Koh, Samuel Sánchez, Sei Kwang Hahn

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Abstract

Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8⁺ T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy.

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含有 STING 激动剂的尿素酶动力纳米马达用于膀胱癌免疫疗法。

大多数非肌层浸润性膀胱癌都是通过经尿道切除术和膀胱内注射免疫治疗药物来治疗的。然而，由于频繁排尿，将治疗药物送入膀胱壁的效率很低，从而导致治疗失败并产生副作用。在此，我们报告了一种含有干扰素基因刺激物（STING）激动剂的尿素酶驱动纳米马达，可有效激活膀胱壁的免疫细胞。在表征之后，我们进行了体外运动分析，并评估了纳米马达在体内的成群行为。膀胱内灌注可使纳米马达有效渗透并保留在膀胱内。此外，我们还证实了含有 STING 激动剂的纳米马达的抗肿瘤效果（94.2% 的抑制率），并在雌性小鼠膀胱癌模型中招募了 CD8+ T 细胞（与 PBS 相比增加了 11.2 倍），增强了抗肿瘤免疫反应。此外，我们还证明，在膀胱癌模型中，含有 STING 激动剂的纳米马达的抗肿瘤效果优于金标准卡介苗疗法和抗 PD-1 抑制剂 pembrolizumab。综上所述，尿素酶驱动的纳米马达将为下一代膀胱癌免疫疗法平台提供一个范例。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.