Biodegradable Carrier-Free Nanomedicine via Self-Assembly of Pure Drug Molecules for Triple Sensitization of Radiotherapy

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2025-04-23 DOI:10.1021/acsnano.4c15736

Rongjun Zhang, Lihao Guo, Qingjiao Li, Yin Liang, Yingying Liao, Huibin Xu, Chutong Liu, Gandong Zhou, Li Wang, Shuxiang Xu, Miaomiao Yuan

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Abstract

Radiotherapy (RT) has been one of the most widely applied cancer treatments, while radiotherapy resistance remains a major limitation. Herein, we synthesized a biodegradable AID nanomedicine incorporating atovaquone (ATO), new indocyanine green (IR820), and doxorubicin (DOX) via π–π stacking and hydrophobic interactions, along with high drug loading efficiency and long-term stability. The AID nanomedicine effectively reduces the activity of mitochondrial electron transport chain complexes I/II/III/IV/V, disrupts the mitochondrial oxidative respiratory chain, and decreases oxygen consumption, thereby alleviating the hypoxic microenvironment within the tumor. Moreover, mild hyperthermia induced by IR820 improves intratumor blood flow, thereby enhancing the radiotherapeutic efficiency. Additionally, DOX-triggered chemotherapy further sensitizes the tumor to radiotherapy, achieving triple sensitization. Our findings demonstrate that AID nanomedicine, combined with near-infrared (NIR) and radiotherapy, significantly suppresses tumor growth in vivo without noticeable side effects. In conclusion, our work presents a self-assembling nanomedicine with excellent biocompatibility, showing great potential for future development in triple radiotherapy sensitization.

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生物可降解的无载体纳米药物通过纯药物分子的自组装用于放射治疗的三重增敏

放疗（RT）已成为应用最广泛的癌症治疗方法之一，但放疗耐药仍然是一个主要限制。本文以阿托瓦醌（ATO）、新吲哚菁绿（IR820）和阿霉素（DOX）为原料，通过π -π堆积和疏水相互作用合成了一种可生物降解的AID纳米药物，具有较高的载药效率和长期稳定性。AID纳米药物可有效降低线粒体电子传递链复合物I/II/III/IV/V的活性，破坏线粒体氧化呼吸链，降低耗氧量，从而缓解肿瘤内缺氧微环境。此外，IR820诱导的轻度热疗可改善肿瘤内血流，从而提高放射治疗效率。此外，dox触发的化疗进一步使肿瘤对放疗增敏，实现三重增敏。我们的研究结果表明，AID纳米药物与近红外（NIR）和放射治疗相结合，在体内显著抑制肿瘤生长，且没有明显的副作用。总之，我们的工作提出了一种具有良好生物相容性的自组装纳米药物，在三联放疗增敏方面具有很大的发展潜力。

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

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.