A Nanoradiosensitizer Potentiates Tumor Radiotherapy through JFK Inhibition and Hypoxia Alleviation

Radiotherapy (RT) is a primary treatment for breast cancer, but its effectiveness is often compromised by hypoxia and intrinsic resistance mechanisms. The F-box protein JFK is overexpressed in breast cancer and is associated with reduced radiosensitivity, but specific JFK inhibitors are currently unavailable. Herein, we developed spherical nanoparticles (SNP-JC) designed to co-deliver small interfering RNA targeting JFK and catalase to the tumor, aiming to silence JFK and alleviate hypoxia to overcome RT resistance. Positron emission tomography imaging demonstrated that SNP-JC efficiently accumulated in the tumors. SNP-JC significantly increased DNA damage in tumor cells after RT and promoted the immunogenic cell death. The combination of SNP-JC and RT activated CD8<sup>+</sup> T cells and elicited a robust antitumor immunity, resulting in suppressed primary tumor growth and reduced lung metastasis. Our findings demonstrate that a nanoplatform capable of simultaneously silencing JFK and mitigating hypoxia can enhance tumor radiosensitivity, improve antitumor efficacy, and prevent metastasis.

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Publication Details

Journal
Nano Letters
Published
2025-03-24
DOI
https://doi.org/10.1021/acs.nanolett.5c00677
Citations
2
Primary Topic
Nanoplatforms for cancer theranostics
Type
article
Field-Weighted Citation Impact
1.35

Funders

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article

A Nanoradiosensitizer Potentiates Tumor Radiotherapy through JFK Inhibition and Hypoxia Alleviation

Xiujie Yang, Jianze Wang, Rui Song, Zhaofei Liu et al.
2 citations
Nano Letters
Nanoplatforms for cancer theranostics
1.35
article

A Nanoradiosensitizer Potentiates Tumor Radiotherapy through JFK Inhibition and Hypoxia Alleviation

Xiujie Yang, Jianze Wang, Rui Song, Zhaofei Liu, Zhi Yang, Feng Wang, Luyang Sun, Mo Li, Kui Li, Lin He, Qianrui Guo, Yameng Hao, Jinhong Du, Haoyi Zhou
article en
2 citations

Abstract

Radiotherapy (RT) is a primary treatment for breast cancer, but its effectiveness is often compromised by hypoxia and intrinsic resistance mechanisms. The F-box protein JFK is overexpressed in breast cancer and is associated with reduced radiosensitivity, but specific JFK inhibitors are currently unavailable. Herein, we developed spherical nanoparticles (SNP-JC) designed to co-deliver small interfering RNA targeting JFK and catalase to the tumor, aiming to silence JFK and alleviate hypoxia to overcome RT resistance. Positron emission tomography imaging demonstrated that SNP-JC efficiently accumulated in the tumors. SNP-JC significantly increased DNA damage in tumor cells after RT and promoted the immunogenic cell death. The combination of SNP-JC and RT activated CD8<sup>+</sup> T cells and elicited a robust antitumor immunity, resulting in suppressed primary tumor growth and reduced lung metastasis. Our findings demonstrate that a nanoplatform capable of simultaneously silencing JFK and mitigating hypoxia can enhance tumor radiosensitivity, improve antitumor efficacy, and prevent metastasis.

Nano LettersVol. 25(13)
Peking University (CN), National Medical Products Administration (CN), Peking University Cancer Hospital (CN), Peking University Third Hospital (CN)
National Natural Science Foundation of China, Peking University, Beijing Municipal Natural Science Foundation, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 21%
Nanoplatforms for cancer theranostics
1.35
DOISourceOpenAlex
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