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新型生物标志物发现偶联血浆疗法增强肿瘤穿透用于宫颈癌非手术治疗

英文原题:Novel biomarker discovery-coupled plasma therapy with enhanced tumor penetration for non-surgical treatment of cervical cancer.

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Novel biomarker discovery-coupled plasma therapy with enhanced tumor penetration for non-surgical treatment of cervical cancer.

PubMed 2025/06/10(内容时间) J Control Release Q1 · IF 12.4(JCR 2025)

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中文摘要

针对年轻宫颈癌患者,对非手术、保留生育功能的治疗需求日益增长。本研究探讨了以生物标志物驱动的非热等离子体(NTP)疗法作为一种具有深部组织穿透能力的局部治疗策略,突出其在可控氧化调节和靶向药物递送方面的潜力。对ROS相关分子的筛选揭示了NTP敏感性与抗氧化酶超氧化物歧化酶1(SOD1)表达之间的关联,并确定人乳头瘤病毒(HPV)癌蛋白E6和p53为上游调控因子。

此外,NTP被证明可影响toll样受体信号9并诱导免疫原性细胞死亡(ICD),增强肿瘤微环境内的局部免疫激活。在异种移植动物肿瘤模型中,SOD1被确定为NTP的潜在生物标志物,而在使用表达HPV16-E6和HPV16-E7的TC-1细胞系的同基因肿瘤模型中,NTP治疗同时表现出抗肿瘤效应和TIL(肿瘤浸润淋巴细胞)的增加。对患者子宫组织中NTP穿透性的评估显示,宫颈癌发生的转化区穿透深度显著大于鳞状区。

值得注意的是,NTP在宫颈癌组织中达到约5 mm的穿透深度,提示其作为局部治疗应用中药物递送增强剂的潜力。这些发现表明,NTP可能作为一种新型非侵入性平台,用于宫颈癌治疗中的可控治疗递送,为传统手术方法提供替代选择。

展开英文摘要原文

There is a growing need for non-surgical, fertility-preserving treatments for young patients with cervical cancer.

This study explores biomarker-driven non-thermal plasma (NTP) therapy as a localized therapeutic strategy with deep tissue penetration, highlighting its potential for controlled oxidative modulation and targeted drug delivery. Screening of ROS-related molecules revealed an association between sensitivity to NTP and the expression of the antioxidant enzyme superoxide dismutase 1 (SOD1), with human papillomavirus (HPV) oncoprotein E6 and p53 identified as upstream regulators.

Additionally, NTP was shown to influence toll-like receptor signaling 9 and induce immunogenic cell death (ICD), enhancing localized immune activation within the tumor microenvironment. In a xenografted animal tumor model, SOD1 was identified as a potential biomarker for NTP, while in a syngeneic tumor model using TC-1 cell lines expressing HPV16-E6 and HPV16-E7, NTP treatment demonstrated both antitumor effects and an increase in tumor-infiltrating lymphocytes.

Evaluation of NTP penetration in patient uterine tissues showed that the depth of penetration was significantly greater in the transformation zone, where cervical cancer occurs, than in the squamous zone.

Notably, NTP reached a penetration depth of ∼5 mm in cervical cancer tissues, suggesting its potential as a drug delivery enhancer for localized therapeutic applications.

These findings suggest that NTP may serve as a novel non-invasive platform for controlled therapeutic delivery in cervical cancer treatment, offering an alternative to conventional surgical approaches.

论文信息

作者
Kim SW、Kang MJ、Kim Y、Hwang WY、Lee A、Le QV、Han I、Jung MH
第一作者单位
Division of Biological Sciences, Sookmyung Women's University, Seoul 04310, South Korea; Research Institute for Women's Health, Sookmyung Women's University, Seoul 04310, South Korea.South Korea
通讯作者单位
Department of Obstetrics & Gynecology, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, South Korea. Electronic address: kbsgyonco@khu.ac.kr.South Korea
文献类型
非美国政府资助研究
期刊
Journal of controlled release : official journal of the Controlled Release Society2025 Aug 10
原文标识
PubMed 40505890 · DOI 10.1016/j.jconrel.2025.113946