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基于负载SO前药的金-银空心纳米三角形用于深部肿瘤治疗时线粒体中Bax上调增强

Enhanced Bax upregulating in mitochondria for deep tumor therapy based on SO prodrug loaded Au-Ag hollow nanotriangles.

作者信息

Xu Min, Lu Qianglan, Song Yilin, Yang Lifang, Li Jining, Li Nan

机构信息

Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, PR China.

Institute of Laser and Optoelectronics, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, 300072, Tianjin, PR China.

出版信息

Biomaterials. 2020 Aug;250:120076. doi: 10.1016/j.biomaterials.2020.120076. Epub 2020 Apr 26.


DOI:10.1016/j.biomaterials.2020.120076
PMID:32361390
Abstract

Nowadays, limited deep tumor penetration and lower therapeutic effect are still the major obstacle in nanomedicines for cancer therapy. Here, we developed high-efficiency nanocomposites, SO prodrug (BTS) loaded Au-Ag hollow nanotriangles (Au-Ag-BTS HTNs), which could not only synergistically upregulate Bax expression in mitochondria, but also be triggered by acidic tumor microenvironment to generate SO for deep tumor therapy. Upon NIR laser irradiation, Au-Ag hollow nanotriangles (Au-Ag HTNs) produced plenty of heat for photothermal therapy (PTT), while the acidic condition in tumor cells induced on-demand SO release from BTS for deep tumor therapy. More importantly, the combined therapy could simultaneously upregulate the expression of apoptosis factor Bax as well as downregulate Bcl-2 in mitochondria, which would induce an increase of Caspase-3 expression to accelerate the apoptosis of tumor cells, thereby achieving a win-win cooperation. The results indicated that enhanced deep tumor therapeutic effect based on Au-Ag-BTS HTNs was realized in vitro and in vivo. Such pH-triggered SO therapy offered a novel strategy for responding tumor microenvironment and improving penetration and heterogeneity distribution of nanotherapeutics in tumor.

摘要

如今,深部肿瘤穿透受限和治疗效果较低仍是纳米药物用于癌症治疗的主要障碍。在此,我们开发了高效纳米复合材料,负载SO前药(BTS)的金-银中空纳米三角形(Au-Ag-BTS HTNs),其不仅能协同上调线粒体中Bax的表达,还能被酸性肿瘤微环境触发产生SO用于深部肿瘤治疗。在近红外激光照射下,金-银中空纳米三角形(Au-Ag HTNs)产生大量热量用于光热治疗(PTT),而肿瘤细胞中的酸性条件诱导BTS按需释放SO用于深部肿瘤治疗。更重要的是,联合治疗可同时上调凋亡因子Bax的表达并下调线粒体中Bcl-2的表达,这将导致Caspase-3表达增加以加速肿瘤细胞凋亡,从而实现双赢。结果表明,基于Au-Ag-BTS HTNs在体外和体内均实现了增强的深部肿瘤治疗效果。这种pH触发的SO治疗为响应肿瘤微环境以及改善纳米治疗剂在肿瘤中的穿透和异质性分布提供了一种新策略。

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引用本文的文献

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Adv Sci (Weinh). 2025-2

[2]
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[3]
A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Adv Sci (Weinh). 2024-4

[4]
Photothermal-Triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence.

Adv Sci (Weinh). 2023-10

[5]
Dopamine multivalent-modified polyaspartic acid for MRI-guided near-infrared photothermal therapy.

Regen Biomater. 2023-3-14

[6]
Near-infrared light-triggered nano-prodrug for cancer gas therapy.

J Nanobiotechnology. 2021-12-23

[7]
Advances in Hollow Inorganic Nanomedicines for Photothermal-Based Therapies.

Int J Nanomedicine. 2021

[8]
A sulfur dioxide polymer prodrug showing combined effect with doxorubicin in combating subcutaneous and metastatic melanoma.

Bioact Mater. 2020-11-10

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