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温和的光热/放射治疗通过 MRI/PA 成像引导的一体化策略增强了铁死亡效应,用于乳腺癌消融。

Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy.

机构信息

Department of Radiology, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Heping District, Shenyang, 110004, China.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

出版信息

J Nanobiotechnology. 2023 May 8;21(1):150. doi: 10.1186/s12951-023-01910-6.


DOI:10.1186/s12951-023-01910-6
PMID:37158923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10169499/
Abstract

BACKGROUND: Nanotheranostics advances anticancer management by providing therapeutic and diagnostic functions, that combine programmed cell death (PCD) initiation and imaging-guided treatment, thus increasing the efficacy of tumor ablation and efficiently fighting against cancer. However, mild photothermal/radiation therapy with imaging-guided precise mediating PCD in solid tumors, involving processes related to apoptosis and ferroptosis, enhanced the effect of breast cancer inhibition is not fully understood. RESULTS: Herein, targeted peptide conjugated gold nano cages, iRGD-PEG/AuNCs@FePt NPs ternary metallic nanoparticles (Au@FePt NPs) were designed to achieve photoacoustic imaging (PAI)/Magnetic resonance imaging (MRI) guided synergistic therapy. Tumor-targeting Au@FePt forms reactive oxygen species (ROS), initiated by X-ray-induced dynamic therapy (XDT) in collaboration with photothermal therapy (PTT), inducing ferroptosis-augmented apoptosis to realize effective antitumor therapeutics. The relatively high photothermal conversion ability of Au@FePt increases the temperature in the tumor region and hastens Fenton-like processes to achieve enhanced synergistic therapy. Especially, RNA sequencing found Au@FePt inducting the apoptosis pathway in the transcriptome profile. CONCLUSION: Au@FePt combined XDT/PTT therapy activate apoptosis and ferroptosis related proteins in tumors to achieve breast cancer ablation in vitro and in vivo. PAI/MRI images demonstrated Au@FePt has real-time guidance for monitoring synergistic anti-cancer therapy effect. Therefore, we have provided a multifunctional nanotheranostics modality for tumor inhibition and cancer management with high efficacy and limited side effects.

摘要

背景:纳米诊疗学通过提供治疗和诊断功能来推进癌症治疗管理,将程序性细胞死亡(PCD)的启动与影像引导的治疗相结合,从而提高肿瘤消融的疗效,并有效地对抗癌症。然而,在实体瘤中,通过影像引导的精确介导 PCD 的温和光热/放射治疗,涉及与细胞凋亡和铁死亡相关的过程,增强了乳腺癌抑制的效果,但其机制尚不完全清楚。

结果:本文设计了靶向肽偶联的金纳米笼、iRGD-PEG/AuNCs@FePt NPs 三元金属纳米颗粒(Au@FePt NPs),以实现超声成像(PAI)/磁共振成像(MRI)引导的协同治疗。肿瘤靶向的 Au@FePt 形成活性氧(ROS),在 X 射线诱导的动态治疗(XDT)与光热治疗(PTT)协同作用下,引发铁死亡增强的细胞凋亡,实现有效的抗肿瘤治疗。Au@FePt 具有较高的光热转换能力,可增加肿瘤区域的温度,并加速芬顿样反应,从而实现增强的协同治疗。特别是,RNA 测序发现 Au@FePt 在转录组图谱中诱导了细胞凋亡途径。

结论:Au@FePt 联合 XDT/PTT 治疗激活了肿瘤中与细胞凋亡和铁死亡相关的蛋白,实现了乳腺癌在体外和体内的消融。PAI/MRI 图像表明,Au@FePt 具有实时监测协同抗癌治疗效果的能力。因此,我们为肿瘤抑制和癌症管理提供了一种多功能的纳米诊疗模式,具有高效和有限的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/f9a4fdf91240/12951_2023_1910_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/f56d2e3a941e/12951_2023_1910_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/b18cdf859af5/12951_2023_1910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/42e8c82eadac/12951_2023_1910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/4a65bbd676e1/12951_2023_1910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/7e1c223543cc/12951_2023_1910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/206e24bbb178/12951_2023_1910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/021c6675b2f7/12951_2023_1910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/914b7c36aeee/12951_2023_1910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/f9a4fdf91240/12951_2023_1910_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/f56d2e3a941e/12951_2023_1910_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/b18cdf859af5/12951_2023_1910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/42e8c82eadac/12951_2023_1910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/4a65bbd676e1/12951_2023_1910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/7e1c223543cc/12951_2023_1910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/206e24bbb178/12951_2023_1910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/021c6675b2f7/12951_2023_1910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/914b7c36aeee/12951_2023_1910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e266/10169499/f9a4fdf91240/12951_2023_1910_Fig8_HTML.jpg

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本文引用的文献

[1]
Tumor-Homing and Immune-Reprogramming Cellular Nanovesicles for Photoacoustic Imaging-Guided Phototriggered Precise Chemoimmunotherapy.

ACS Nano. 2022-10-25

[2]
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A biomass-derived Schiff base material composited with polylactic acid nanofiber membrane as selective fluorescent 'turn off/on' platform for Pb quantitative detection and characterization.

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Chemodynamic and Photothermal Combination Therapy Based on Dual-Modified Metal-Organic Framework for Inducing Tumor Ferroptosis/Pyroptosis.

ACS Appl Mater Interfaces. 2022-6-1

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pH-Triggered Poly(ethylene glycol)-Poly(lactic acid/glycolic acid)/Croconaine Nanoparticles-Assisted Multiplexed Photoacoustic Imaging and Enhanced Photothermal Cancer Therapy.

ACS Appl Bio Mater. 2021-5-17

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Targeting regulated cell death in tumor nanomedicines.

Theranostics. 2022

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