Manganese-doped liquid metal nanoplatforms for cellular uptake and glutathione depletion-enhanced photothermal and chemodynamic combination tumor therapy

IF 9.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia Pub Date : 2025-01-01 DOI:10.1016/j.actbio.2024.11.010

Shuai Wang , Yang Zou , Liefeng Hu , Yonggang Lv

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引用次数: 0

Abstract

Chemodynamic therapy (CDT) involves the catalysis of in situ overexpressed hydrogen peroxide (H₂O₂) into highly toxic reactive oxygen species (ROS) to treat tumors. However, the efficacy of CDT is greatly hampered by limited cellular internalization efficiency, ROS scavenging by glutathione (GSH), and slow reaction rate. To overcome the current limitations of CDT, a manganese-doped and polyethylene glycol (PEG)-modified liquid metal (LM)-silica nanoplatform (labeled as Mn-LMOP) with varying stiffness is constructed to achieve synergistic photothermal therapy (PTT) and CDT, which can further induce immunogenic cell death (ICD) in tumors to enhance the anti-tumour effects. Significantly, benefiting from the increased stiffness, the Mn-LMOP nanoparticles (NPs) can enhance cellular uptake and lysosomal escape, and gradually accumulate in tumor sites. Moreover, manganese-doped NPs exhibite good photothermal effects and can rapidly reacte with intratumoral GSH to produce Mn²⁺, inhibiting GSH-mediated ROS clearance and promoting the efficiency of CDT. This combined treatment strategy can activate the immune response of the tumors, which holds the promise of photothermal/chemodynamic/immune multimodal therapeutic effects. This LM-based nanosystem will provide a paradigm for enhanced CDT/PTT combination anti-tumour efficacy.

Statement of significance

Chemodynamic therapy (CDT) is a promising drug-free treatment approach characterized by its low invasiveness and minimal side effect. However, CDT encounters challenges such as high levels of glutathione (GSH), low Fenton-like reaction rate, and inefficient cellular uptake in tumor tissues. Here, a manganese-doped liquid metal (LM) nanomaterial was designed to achieve synergistic photothermal therapy (PTT) and CDT. This innovative strategy enhanced cellular uptake by adjusting the mechanical property of nanoparticles (NPs) and facilitated the consumption of GSH, while simultaneously accelerating the Fenton-like reaction rate with the assistance of PTT-mediated hyperthermia. This combined CDT/PTT strategy also activated the immune response within the tumor, demonstrating significant therapeutic potential.

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掺锰液态金属纳米平台用于细胞摄取和谷胱甘肽耗竭增强型光热和化学动力联合肿瘤疗法。

化学动力疗法（CDT）是指将原位过表达的过氧化氢（H2O2）催化成高毒性活性氧（ROS）来治疗肿瘤。然而，由于细胞内化效率有限、谷胱甘肽（GSH）对 ROS 的清除作用以及反应速度缓慢，CDT 的疗效大受影响。为了克服目前 CDT 的局限性，研究人员构建了一种掺锰和聚乙二醇（PEG）修饰的具有不同硬度的液态金属（LM）-二氧化硅纳米平台（标记为 Mn-LMOP），以实现光热疗法（PTT）和 CDT 的协同作用，从而进一步诱导肿瘤中的免疫原性细胞死亡（ICD），增强抗肿瘤效果。值得注意的是，锰-LMOP 纳米粒子（NPs）得益于硬度的增加，可以提高细胞摄取和溶酶体逃逸能力，并在肿瘤部位逐渐积累。此外，掺锰的 NPs 具有良好的光热作用，并能迅速与瘤内 GSH 反应生成 Mn2+，从而抑制 GSH 介导的 ROS 清除，提高 CDT 的效率。这种联合治疗策略可以激活肿瘤的免疫反应，有望实现光热/化学动力/免疫多模式治疗效果。这种基于 LM 的纳米系统将为增强 CDT/PTT 联合抗肿瘤疗效提供一个范例。意义说明：化学动力疗法（CDT）是一种前景广阔的无药治疗方法，其特点是创伤小、副作用小。然而，化学动力疗法也遇到了一些挑战，如谷胱甘肽（GSH）含量高、芬顿反应速率低、肿瘤组织细胞吸收效率低等。在此，我们设计了一种掺锰液态金属（LM）纳米材料，以实现光热疗法（PTT）和CDT的协同作用。这种创新策略通过调整纳米颗粒（NPs）的机械性能增强了细胞吸收，促进了GSH的消耗，同时在PTT介导的热效应的帮助下加快了芬顿反应速率。这种 CDT/PTT 组合策略还激活了肿瘤内的免疫反应，显示出巨大的治疗潜力。

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来源期刊

Acta Biomaterialia 工程技术-材料科学：生物材料

CiteScore

16.80

自引率

3.10%

发文量

776

审稿时长

30 days

期刊介绍： Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.