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用于靶向结直肠癌治疗的ROS/酶双响应药物递送系统：协同化疗、抗炎和肠道微生物群调节

ROS/Enzyme Dual-Responsive Drug Delivery System for Targeted Colorectal Cancer Therapy: Synergistic Chemotherapy, Anti-Inflammatory, and Gut Microbiota Modulation.

作者信息

Zhang Xin, Lian Ruonan, Fan Bingbing, Meng Lei, Zhang Pengxia, Zhang Yu, Sun Weitong

机构信息

College of Pharmacy, Jiamusi University, Xiangyang District, Jiamusi 154007, China.

Heilongjiang Center for Drug Evaluation and Inspection, Harbin 150000, China.

出版信息

Pharmaceutics. 2025 Jul 21;17(7):940. doi: 10.3390/pharmaceutics17070940.

DOI:10.3390/pharmaceutics17070940
PMID:40733148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12300498/
Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system's ability to disrupt the "inflammation-microbiota-tumor" axis. The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC.

摘要

结直肠癌（CRC）是癌症相关死亡的主要原因，由慢性炎症、肠道微生物群失调和复杂的肿瘤微环境相互作用驱动。目前的治疗方法受到全身毒性和肿瘤蓄积性差的限制。本研究旨在开发一种ROS/酶双响应口服给药系统，即魔芋葡甘聚糖-姜黄素/聚水杨酸甲酯微球（KGM-CUR/PSM微球），以实现结直肠癌中药物的精确释放，并增强肿瘤特异性药物蓄积，该系统利用了结直肠癌中较高的ROS水平以及结直肠组织中β-甘露聚糖酶的过表达。在本研究中，我们通过硫醚键将聚乙二醇单甲醚（mPEG）和柳氮磺胺吡啶（MSL）偶联，合成了一种ROS响应前药聚合物（PSM）。然后采用薄膜水化法将姜黄素（CUR）包裹在PSM中，形成肿瘤微环境响应性胶束（CUR/PSM）。随后，使用魔芋葡甘聚糖（KGM）制备KGM-CUR/PSM微球，实现结直肠癌治疗的靶向给药。通过体外药物释放研究证实了ROS/酶双响应特性。在SW480细胞中评估了细胞毒性、细胞摄取和细胞迁移。在AOM/DSS诱导的结直肠癌小鼠中评估了体内疗效，监测肿瘤生长、炎症标志物（TNF-α、IL-1β、IL-6、MPO）和肠道微生物群组成。体外药物释放研究表明，KGM-CUR/PSM微球呈现出ROS/酶响应释放曲线。CUR/PSM胶束在细胞毒性试验、细胞摄取研究和细胞迁移试验中显示出显著的抗结直肠癌疗效。在AOM/DSS诱导的结直肠癌小鼠中，KGM-CUR/PSM微球显著提高了生存率，抑制了结直肠癌肿瘤生长，并有效降低了炎症细胞因子（TNF-α、IL-1β、IL-6）和髓过氧化物酶（MPO）的表达。组织病理学和微生物学分析显示，KGM-CUR/PSM组的结肠结构和微生物多样性接近正常，证实了该系统破坏“炎症-微生物群-肿瘤”轴的能力。KGM-CUR/PSM微球通过诱导细胞凋亡、减轻炎症和调节肠道微生物群，显示出抗肿瘤疗效的协同增强，为未来结直肠癌的临床治疗提供了一种有前景的刺激响应给药系统。

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本文引用的文献

1
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2
Dual approach: micellar delivery of chlorambucil prodrug with concurrent glutathione depletion and GST inhibition for enhanced anticancer activity.双重策略：用胶束递药法传递苯丁酸氮芥前药，同时耗竭谷胱甘肽并抑制 GST，以增强抗癌活性。
Nanotechnology. 2024 Jun 7;35(34). doi: 10.1088/1361-6528/ad501a.
3
Construction of intelligent drug delivery system based on polysaccharide-derived polymer micelles: A review.
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Int J Biol Macromol. 2024 Jan;254(Pt 3):128048. doi: 10.1016/j.ijbiomac.2023.128048. Epub 2023 Nov 13.
4
Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer.美沙拉嗪的抗肿瘤作用机制及其在结直肠癌预防中的潜在作用。
Molecules. 2023 Jun 29;28(13):5081. doi: 10.3390/molecules28135081.
5
Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives.响应型纳米系统在溃疡性结肠炎靶向治疗中的应用：现状与未来展望。
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6
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Drug Deliv Transl Res. 2023 Nov;13(11):2767-2789. doi: 10.1007/s13346-023-01368-x. Epub 2023 Jun 6.
7
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Nat Rev Clin Oncol. 2023 Jul;20(7):429-452. doi: 10.1038/s41571-023-00766-x. Epub 2023 May 11.
8
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9
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