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用于乳腺癌自扩增肿瘤治疗的 pH/GSH 双重响应纳米粒子。

pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.

机构信息

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan Province, 450046, P. R. China.

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, Henan Province, 450001, P.R. China.

出版信息

J Nanobiotechnology. 2024 Jun 10;22(1):324. doi: 10.1186/s12951-024-02588-0.

DOI:10.1186/s12951-024-02588-0
PMID:38858692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11163783/
Abstract

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

摘要

乳腺癌仍然是一种对全球人类健康构成严重威胁的恶性肿瘤。化疗是临床实践中最广泛有效的癌症治疗方法之一，但它存在一些缺点，如靶向性差、毒性高、副作用多、易产生耐药性等。对于自动放大肿瘤治疗，通过用单宁酸（TA）-Fe（III）涂层包裹负载藤黄酸（GA）的树枝状多孔硅纳米粒子（DPSNs）来制备纳米颗粒 GDTF。GDTF 具有近红外（NIR）增强和 pH/谷胱甘肽（GSH）双重响应药物释放、光热转换、GSH 耗竭和羟基自由基（·OH）产生的特性。当 GDTF 暴露于近红外激光照射下时，它可以在体外和体内有效抑制细胞增殖和肿瘤生长，同时具有有限的毒性。这可能是由于增强的肿瘤积累、活性氧（ROS）产生、GSH 耗竭和 TrxR 活性降低的协同作用所致。本研究突出了自动放大肿瘤治疗的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/5539a52683fc/12951_2024_2588_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/eb8b362d37f5/12951_2024_2588_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/0ff1285e8e02/12951_2024_2588_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/50d6a8a6605c/12951_2024_2588_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/a0bb7a3fcafc/12951_2024_2588_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/9aa7cfa259a4/12951_2024_2588_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/18c006c5bc64/12951_2024_2588_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/db8240008452/12951_2024_2588_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/068ccae616c0/12951_2024_2588_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/5539a52683fc/12951_2024_2588_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/eb8b362d37f5/12951_2024_2588_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/0ff1285e8e02/12951_2024_2588_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/50d6a8a6605c/12951_2024_2588_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/a0bb7a3fcafc/12951_2024_2588_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/9aa7cfa259a4/12951_2024_2588_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/18c006c5bc64/12951_2024_2588_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/db8240008452/12951_2024_2588_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/068ccae616c0/12951_2024_2588_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f2/11163783/5539a52683fc/12951_2024_2588_Fig9_HTML.jpg

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pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.

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[1]
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Int J Nanomedicine. 2025-6-28

[2]
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本文引用的文献

[1]
Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer.

Research (Wash D C). 2023-10-3

[2]
Unimolecular Self-Assembled Hemicyanine-Oleic Acid Conjugate Acts as a Novel Succinate Dehydrogenase Inhibitor to Amplify Photodynamic Therapy and Eliminate Cancer Stem Cells.

Research (Wash D C). 2023-9-6

[3]
Recent advances in targeted strategies for triple-negative breast cancer.

J Hematol Oncol. 2023-8-28

[4]
Lactoferrin-Modified Gambogic Acid Liposomes for Colorectal Cancer Treatment.

Mol Pharm. 2023-8-7

[5]
NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating against Multidrug Resistance and Metastasis.

Small. 2023-4

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CA Cancer J Clin. 2023-1

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Synergistic chemotherapy and phototherapy based on red blood cell biomimetic nanomaterials.

J Control Release. 2022-12

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Gambogenic acid induces apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress via JNK pathway in prostate cancer cells.

Phytother Res. 2023-1

[9]
Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy.

ACS Nano. 2022-9-27

[10]
Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review.

Drug Deliv. 2022-12

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