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核心技术专利:CN118964589B侵权必究
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一种持续有效的供氧策略,用于长期调节缺氧肿瘤微环境,以增强长效放射性核素内治疗。

A continuously efficient O-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

出版信息

J Nanobiotechnology. 2024 Jan 3;22(1):7. doi: 10.1186/s12951-023-02268-5.


DOI:10.1186/s12951-023-02268-5
PMID:38166931
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10763042/
Abstract

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous HO to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous HO into O to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

摘要

放射性核素内放疗(RIT)是一种临床有效的癌症治疗方法,但由于肿瘤微环境(TME)的缺氧特性,其治疗效果仍不理想。过氧化氢酶(CAT)或类 CAT 纳米材料可用于酶促分解 TME 内源性 HO,以促进 TME 氧合,从而减轻肿瘤内的缺氧水平,但由于其稳定性或降解性差,缺氧缓解的持续时间较短,仍然阻碍了其有效性,无法与 RIT 的长期治疗时间相匹配。在此,我们提出了一种利用面依赖性类 CAT 的 Pd 基二维(2D)纳米平台来持续增强 RIT 的创新策略。具体而言,合理设计的 2D Pd@Au 纳米片(NSs)能够持续将内源性 HO 酶促转化为 O,从而克服缺氧诱导的 RIT 耐药性。此外,部分包覆的 Au 层赋予了近红外二区(NIR-II)响应性和适度的光热治疗,增强了它们的酶促功能。这种具有双重作用的方法为重塑 TME 铺平了道路,从而促进了近距离放射疗法对癌症的消融。我们的工作在催化纳米医学和核医学的整合方面取得了重大进展,其总体目标是放大接受 RIT 治疗的患者的临床获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/b6ff0fc010b2/12951_2023_2268_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/911426f6ef38/12951_2023_2268_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/fe4bde04127a/12951_2023_2268_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/50a994106321/12951_2023_2268_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/64b06b31b6a8/12951_2023_2268_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/b6ff0fc010b2/12951_2023_2268_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/911426f6ef38/12951_2023_2268_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/fe4bde04127a/12951_2023_2268_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/50a994106321/12951_2023_2268_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/64b06b31b6a8/12951_2023_2268_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c1/10763042/b6ff0fc010b2/12951_2023_2268_Fig4_HTML.jpg

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A continuously efficient O-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

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引用本文的文献

[1]
Radionuclide-labeled nanomaterials for tumor therapy: Recent progress and perspectives.

Mater Today Bio. 2025-8-5

[2]
Hypoxia-augmented chemotherapy potentiates imaging-guided combinatorial radionuclide-sonodynamic therapy for pancreatic cancer.

J Nanobiotechnology. 2025-7-24

本文引用的文献

[1]
Near-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury.

Nat Commun. 2023-1-13

[2]
Fluorination Enhances NIR-II Emission and Photothermal Conversion Efficiency of Phototheranostic Agents for Imaging-Guided Cancer Therapy.

Adv Mater. 2023-1

[3]
Tumor oxygenation nanoliposome synergistic hypoxia-inducible-factor-1 inhibitor enhanced Iodine-125 seed brachytherapy for esophageal cancer.

Biomaterials. 2022-10

[4]
Multifunctional nanotheranostics for near infrared optical imaging-guided treatment of brain tumors.

Adv Drug Deliv Rev. 2022-11

[5]
Catalase-Like Nanozymes: Classification, Catalytic Mechanisms, and Their Applications.

Small. 2022-9

[6]
Edge-Site Engineering of Defective Fe-N Nanozymes with Boosted Catalase-Like Performance for Retinal Vasculopathies.

Adv Mater. 2022-9

[7]
An NIR-II Photothermally Triggered "Oxygen Bomb" for Hypoxic Tumor Programmed Cascade Therapy.

Adv Mater. 2022-7

[8]
Nanomedicine potentiates mild photothermal therapy for tumor ablation.

Asian J Pharm Sci. 2021-11

[9]
Radioactive nano-oxygen generator enhance anti-tumor radio-immunotherapy by regulating tumor microenvironment and reducing proliferation.

Biomaterials. 2022-1

[10]
Biomaterial-mediated internal radioisotope therapy.

Mater Horiz. 2021-5-1

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