A pyroptosis proportion tunable nano-modulator for cancer immunotherapy.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-07-25 eCollection Date: 2025-01-01 DOI:10.7150/thno.112209
Zhuang Chen, Zuo Yang, Zhiping Rao, Yi Luo, Weijing Liu, Chaoqiang Qiao, Qian Jia, Peng Yang, Ruili Zhang, Zhongliang Wang
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引用次数: 0

Abstract

Rationale: Pyroptosis, a form of programmed cell death mediated by gasdermin proteins, holds significant potential in cancer immunotherapy. However, precise control of pyroptosis in cancer cells is essential to avoid biosafety concerns. This study aimed to develop a tumor-targeted and tunable pyroptosis-inducing strategy to enhance antitumor efficacy while minimizing systemic side effects. Methods: An innovative H2S-activated nanomodulator equipped with an optical switch was designed for tumor-specific and adjustable pyroptosis induction. The nanomodulator was activated by H2S in the tumor microenvironment of colorectal cancer and further regulated by laser irradiation. Gasdermin-E-mediated pyroptosis was triggered through the synergistic effects of photothermal temperature modulation and demethylation. The proportion of cells undergoing pyroptosis was precisely controlled within a tunable range. Results: The nanomodulator successfully induced pyroptosis in microsatellite-stable colorectal cancer cells within a tunable range of 0-31%. This precise regulation significantly enhanced antitumor efficacy while minimizing systemic side effects. The combination of photothermal modulation and demethylation ensured effective and safe pyroptosis induction. Conclusions: This study presents a novel and precise method for controlling pyroptosis using photothermal temperature modulation. The findings provide essential guidance for in vivo applications and offer valuable insights into the development of nanomedicines capable of safely and effectively inducing adjustable proportion of pyroptosis in cancer therapy.

一种用于癌症免疫治疗的焦亡比例可调纳米调节剂。
原理:焦亡是一种由气皮蛋白介导的程序性细胞死亡形式,在癌症免疫治疗中具有重要的潜力。然而,精确控制癌细胞的焦亡对于避免生物安全问题至关重要。本研究旨在开发一种肿瘤靶向和可调节的热诱导策略,以提高抗肿瘤疗效,同时最大限度地减少全身副作用。方法:设计了一种具有光开关的h2s激活纳米调节剂,用于肿瘤特异性和可调节的焦亡诱导。该纳米调节剂在结直肠癌肿瘤微环境中被H2S激活,并通过激光照射进一步调控。通过光热温度调节和去甲基化的协同作用触发气凝胶- e介导的热亡。发生焦亡的细胞比例被精确控制在可调范围内。结果:纳米调节剂成功诱导微卫星稳定的结直肠癌细胞在0-31%的可调范围内焦亡。这种精确的调节显着提高了抗肿瘤疗效,同时最大限度地减少了全身副作用。光热调制和去甲基化的结合确保了有效和安全的热亡诱导。结论:本研究提出了一种利用光热温度调制控制焦亡的新方法。这些发现为体内应用提供了重要的指导,并为开发能够安全有效地诱导可调比例焦亡的纳米药物提供了宝贵的见解。
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
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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