Interfering biosynthesis by nanoscale metal-organic frameworks for enhanced radiation therapy

Zi Fu; Zhuang Liu; Jiaxing Wang; Lianfu Deng; Han Wang; Wei Tang; Dalong Ni

doi:10.1016/j.biomaterials.2023.122035

Interfering biosynthesis by nanoscale metal-organic frameworks for enhanced radiation therapy

Biomaterials. 2023 Apr:295:122035. doi: 10.1016/j.biomaterials.2023.122035. Epub 2023 Feb 2.

Authors

Zi Fu¹, Zhuang Liu², Jiaxing Wang³, Lianfu Deng¹, Han Wang⁴, Wei Tang⁵, Dalong Ni⁶

Affiliations

¹ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
³ Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
⁴ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wanghan2021@sjtu.edu.cn.
⁵ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: tangwei105@163.com.
⁶ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: ndl12353@rjh.com.cn.

PMID: 36764193
DOI: 10.1016/j.biomaterials.2023.122035

Abstract

Radiation therapy (RT) is one of the most widely used cancer treatments. However, the vigorous biosynthesis of cancer cells plays an important role for RT resistance. Herein, we develop a hafnium-based nanoscale metal-organic frameworks (Hf-nMOFs) loaded with 3-bromopyruvate (3-BrPA) to overcome RT resistance and achieve favorable RT efficacy. The deposition of X-rays is greatly enhanced by Hf-nMOFs to induce stronger damage to DNA in RT. Simultaneously, as an inhibitor of glycolysis, the loaded 3-BrPA can reduce the supply of energy and interfere with the biosynthesis of proteins to decrease the DNA damage repair. As a result, the 3-BrPA@Hf-nMOFs (BHT) will overcome the RT resistance and enhance the curative effect of RT. Up and down-regulated genes as well as the related pathways in cellular metabolism and biosynthesis are well investigated to reveal the radiosensitization mechanism of BHT. In addition, the Hf element endows BHT with CT imaging capability to real-timely monitor the therapeutic process. Hence, the designed strategy of biosynthesis-targeted radiosensitization could decrease the doses of ionizing radiations and provide fresh perspectives on cancer treatment.

Keywords: Biosynthesis; Glycolysis; Metal-organic frameworks; Nanomedicine; Radiation therapy; Radiosensitization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA
Metal-Organic Frameworks* / pharmacology

Substances

Metal-Organic Frameworks
DNA