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载级联体系的氯 e6 固载、聚多巴胺包覆的中空多孔氧化铈缺氧耐受纳米酶的体外协同光动力、光热、化学动力学和饥饿治疗性能

In Vitro Synergistic Photodynamic, Photothermal, Chemodynamic, and Starvation Therapy Performance of Chlorin e6 Immobilized, Polydopamine-Coated Hollow, Porous Ceria-Based, Hypoxia-Tolerant Nanozymes Carrying a Cascade System.

机构信息

Bioengineering Division, Hacettepe University, Ankara 06800, Turkey.

Graduate School of Science and Engineering, Hacettepe University, Ankara 06800, Turkey.

出版信息

ACS Appl Bio Mater. 2024 May 20;7(5):2781-2793. doi: 10.1021/acsabm.3c01181. Epub 2024 Feb 21.


DOI:10.1021/acsabm.3c01181
PMID:38380497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11110068/
Abstract

A synergistic therapy agent (STA) with photothermal, photodynamic, chemodynamic, and starvation therapy (PTT, PDT, CDT, and ST) functions was developed. Hollow, mesoporous, and nearly uniform CeO nanoparticles (H-CeO NPs) were synthesized using a staged shape templating sol-gel protocol. Chlorin e6 (Ce6) was adsorbed onto H-CeO NPs, and a thin polydopamine (PDA) layer was formed on Ce6-adsorbed H-CeO NPs. Glucose oxidase (GOx) was bound onto PDA-coated Ce6-adsorbed H-CeO NPs to obtain the targeted STA (H-CeO@Ce6@PDA@GOx NPs). A reversible photothermal conversion behavior with the temperature elevations up to 34 °C was observed by NIR laser irradiation at 808 nm. A cascade enzyme system based on immobilized GOx and intrinsic catalase-like activity of H-CeO NPs was rendered on STA for enhancing the effectiveness of PDT by elevation of ROS generation and alleviation of hypoxia in a tumor microenvironment. Glucose-mediated generation of highly toxic hydroxyl radicals (OH) was evaluated for CDT. The effectiveness of PDT on glioblastoma T98G cells was markedly enhanced by O generation started by the decomposition of glucose. A similar increase in cell death was also observed when ST and CDT functions were enhanced by photothermal action. The viability of T98G cells decreased to 10.6% by in vitro synergistic action including ST, CDT, PDT, and PTT without using any antitumor agent.

摘要

一种具有光热、光动力、化学动力学和饥饿治疗(PTT、PDT、CDT 和 ST)功能的协同治疗剂(STA)被开发出来。采用阶段模板溶胶-凝胶法合成了具有中空、介孔和近均一结构的 CeO 纳米粒子(H-CeO NPs)。氯乙锭(Ce6)被吸附到 H-CeO NPs 上,在 Ce6 吸附的 H-CeO NPs 上形成了一层薄的聚多巴胺(PDA)层。葡萄糖氧化酶(GOx)结合到 PDA 涂层的 Ce6 吸附的 H-CeO NPs 上,得到了靶向 STA(H-CeO@Ce6@PDA@GOx NPs)。在 808nm 的近红外激光照射下,观察到具有可逆光热转换行为的温度升高可达 34°C。基于固定化 GOx 和 H-CeO NPs 固有类过氧化物酶活性的级联酶系统被用于 STA,通过提高 ROS 的产生和减轻肿瘤微环境中的缺氧来增强 PDT 的效果。评估了 STA 中葡萄糖介导的产生高毒性羟基自由基(OH)的能力,用于 CDT。通过葡萄糖分解引发的 O 的产生,显著增强了 PDT 对神经胶质瘤 T98G 细胞的效果。当通过光热作用增强 ST 和 CDT 功能时,也观察到细胞死亡的类似增加。在没有使用任何抗肿瘤药物的情况下,体外协同作用(包括 ST、CDT、PDT 和 PTT)使 T98G 细胞的存活率降低至 10.6%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/4b25fda359b9/mt3c01181_0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/e89dccb7f55b/mt3c01181_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/84091d85e593/mt3c01181_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/fe69610ed0de/mt3c01181_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/4b25fda359b9/mt3c01181_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/6765ddbeb5a5/mt3c01181_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/39cae89fd062/mt3c01181_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/c9120db23446/mt3c01181_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/181b06e3b049/mt3c01181_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/e89dccb7f55b/mt3c01181_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/84091d85e593/mt3c01181_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/fe69610ed0de/mt3c01181_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df8/11110068/4b25fda359b9/mt3c01181_0008.jpg

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[2]
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[3]
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ACS Appl Mater Interfaces. 2023-6-14

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Intelligent PdBi@CeO Nanosystem with Dual-Enzyme-Mimetic Activities for Cancer Hypoxia Relief and Synergistic Photothermal/Photodynamic/Chemodynamic Therapy.

ACS Appl Mater Interfaces. 2023-5-10

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Multifunctional manganese oxide-based nanocomposite theranostic agent with glucose/light-responsive singlet oxygen generation and dual-modal imaging for cancer treatment.

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Amplification of oxidative stress with a hyperthermia-enhanced chemodynamic process and MTH1 inhibition for sequential tumor nanocatalytic therapy.

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The direct catalytic synthesis of ultrasmall CuO-coordinated carbon nitrides on ceria for multimodal antitumor therapy.

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[8]
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[9]
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