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IR808-ATIPA:一种用于宫颈癌治疗中增强计算机断层扫描成像及放疗增敏的双功能试剂。

IR808-ATIPA: A Dual-Function Agent for Enhanced Computed Tomography Imaging and Radiotherapy Sensitization in Cervical Cancer Treatment.

作者信息

Liu Kejin, Zuo Rourou, Wang Zhe, Chen Guoliang, Bao Xuefei, Wang Hongbo, Sun Hongzan

机构信息

Liaoning Provincial Key Laboratory of Medical Imaging, Shenyang, China.

Department of Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Biomater Res. 2025 Aug 18;29:0222. doi: 10.34133/bmr.0222. eCollection 2025.


DOI:10.34133/bmr.0222
PMID:40831788
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12358750/
Abstract

Radiotherapy is pivotal in localized cancer treatment, yet balancing therapeutic efficacy with collateral tissue damage remains challenging. Conventional iodinated contrast agents, limited by rapid metabolism and short imaging windows, hinder precise radiotherapy planning. We developed IR808-ATIPA, a tumor microenvironment-responsive iodine-based compound integrating computed tomography (CT) imaging and radiosensitization. Synthesized by covalently linking IR808 and ATIPA, IR808-ATIPA leverages iodine's x-ray attenuation for high-contrast imaging while enhancing radiation dose deposition in cervical cancer. Unlike conventional agents, its prolonged tumor retention improves imaging accuracy and therapeutic targeting. Evaluations in HeLa tumor-bearing nude mice demonstrated superior in vitro/in vivo imaging performance and sustained tumor accumulation. RNA sequencing revealed that IR808-ATIPA enhances radiotherapy efficacy by activating the ferroptosis pathway via increased reactive oxygen species production and amplified x-ray absorption. Safety assessments confirmed no notable toxicity to major organs. IR808-ATIPA functions dually as a CT contrast agent for precise tumor delineation and a radiosensitizer promoting ferroptosis-mediated radiotherapy enhancement. Its extended intratumoral retention enables targeted therapy, minimizing off-target effects. These findings highlight IR808-ATIPA as a promising theranostic agent, bridging imaging-guided precision and therapeutic efficacy to advance personalized cancer treatment.

摘要

放射治疗在局部癌症治疗中起着关键作用,但要在治疗效果与周围组织损伤之间取得平衡仍然具有挑战性。传统的碘化造影剂受限于快速代谢和较短的成像窗口,阻碍了精确的放射治疗计划。我们开发了IR808-ATIPA,一种整合了计算机断层扫描(CT)成像和放射增敏作用的肿瘤微环境响应性碘基化合物。IR808-ATIPA通过将IR808和ATIPA共价连接而合成,利用碘的X射线衰减进行高对比度成像,同时增强宫颈癌中的辐射剂量沉积。与传统造影剂不同,其在肿瘤中的长时间滞留提高了成像准确性和治疗靶向性。对荷HeLa肿瘤裸鼠的评估显示出优异的体外/体内成像性能和持续的肿瘤蓄积。RNA测序表明,IR808-ATIPA通过增加活性氧生成和放大X射线吸收来激活铁死亡途径,从而提高放射治疗效果。安全性评估证实对主要器官无明显毒性。IR808-ATIPA兼具精确肿瘤描绘的CT造影剂和促进铁死亡介导的放射治疗增强的放射增敏剂双重功能。其在肿瘤内的延长滞留实现了靶向治疗,将脱靶效应降至最低。这些发现突出了IR808-ATIPA作为一种有前景的诊疗试剂,弥合成像引导的精准性和治疗效果,以推进个性化癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/2587329ba912/bmr.0222.fig.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/1d02e2d7d919/bmr.0222.fig.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/dd61bd422cce/bmr.0222.fig.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/b625286b2b21/bmr.0222.fig.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/a307ca3fcab5/bmr.0222.fig.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/bec6b7669dc7/bmr.0222.fig.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/9fd660fdfe96/bmr.0222.fig.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/2587329ba912/bmr.0222.fig.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/1d02e2d7d919/bmr.0222.fig.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/dd61bd422cce/bmr.0222.fig.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/b625286b2b21/bmr.0222.fig.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/a307ca3fcab5/bmr.0222.fig.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/bec6b7669dc7/bmr.0222.fig.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/9fd660fdfe96/bmr.0222.fig.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c947/12358750/2587329ba912/bmr.0222.fig.007.jpg

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IR808-ATIPA: A Dual-Function Agent for Enhanced Computed Tomography Imaging and Radiotherapy Sensitization in Cervical Cancer Treatment.

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本文引用的文献

[1]
Inhibition of ferroptosis counteracts the advanced maternal age-induced oocyte deterioration.

Cell Death Differ. 2025-2-6

[2]
Feasibility of dose calculation for treatment plans using electron density maps from a novel dual-layer detector spectral CT simulator.

Radiat Oncol. 2024-7-24

[3]
Survey on fan-beam computed tomography for radiotherapy: Imaging for dose calculation and delineation.

Phys Imaging Radiat Oncol. 2023-12-6

[4]
Therapeutic application of manganese-based nanosystems in cancer radiotherapy.

Biomaterials. 2023-11

[5]
Advances in the study of the molecular biological mechanisms of radiation-induced brain injury.

Am J Cancer Res. 2023-8-15

[6]
Prospects of nanoparticle-based radioenhancement for radiotherapy.

Mater Horiz. 2023-10-2

[7]
A MOF-Based Potent Ferroptosis Inducer for Enhanced Radiotherapy of Triple Negative Breast Cancer.

ACS Nano. 2023-7-25

[8]
Application of nano-radiosensitizers in combination cancer therapy.

Bioeng Transl Med. 2023-2-10

[9]
Clustered Cobalt Nanodots Initiate Ferroptosis by Upregulating Heme Oxygenase 1 for Radiotherapy Sensitization.

Small. 2023-3

[10]
The Role of Positron Emission Tomography and Computed Tomographic (PET/CT) Imaging for Radiation Therapy Planning: A Literature Review.

Diagnostics (Basel). 2022-12-24

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