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Engineered bacterium-metal-organic framework biohybrids for boosting radiotherapy with multiple effects.

Jia-Wei Wang¹, Ping Ji², Jin-Yue Zeng²

¹Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, PR China; Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China.

|October 24, 2024

Summary

This summary is machine-generated.

This study introduces a novel biohybrid platform, SO@Hf-MOF-Pt, for enhancing radiotherapy. It effectively reshapes the tumor microenvironment by metabolizing lactate and generating oxygen, thereby improving therapeutic outcomes.

Keywords:

Biohybrid platform Hypoxia microenvironment Lactate metabolism Radiosentization Tumor therapy

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Area of Science:

Biomedical Engineering
Nanotechnology
Cancer Therapy

Background:

Tumor microenvironments with high hypoxia and lactate levels impede radiotherapy efficacy.
Hypoxia-inducible factor (HIF-1α) and lactate dehydrogenase A (LDHA) play critical roles in this suppressive microenvironment.

Purpose of the Study:

To develop an engineered biohybrid platform for enhancing radiotherapy by targeting the tumor microenvironment.
To investigate the synergistic effects of platinum nanoparticles, hafnium metal-organic frameworks, and Shewanella oneidensis MR-1 in radiosensitization.

Main Methods:

Construction of a biohybrid platform (SO@Hf-MOF-Pt) integrating Shewanella oneidensis MR-1 with Hf-MOF-Pt nanoparticles.
Utilizing the tumor-targeting and metabolic respiration of SO to downregulate HIF-1α by metabolizing lactate.
Leveraging the reaction of SO@Hf-MOF-Pt with hydrogen peroxide to generate oxygen, further inhibiting HIF-1α and LDHA, thus reducing lactate production.

Main Results:

The SO@Hf-MOF-Pt platform successfully enriched in tumor sites.
Metabolic regulation by SO and nanoparticle-mediated oxygen generation effectively relieved tumor hypoxia and reduced lactate levels.
Significant potentiation of radiosensitization and amplification of radiotherapy therapeutic outcomes were observed.

Conclusions:

The engineered biohybrid SO@Hf-MOF-Pt platform demonstrates a promising strategy for overcoming the radio-resistant tumor microenvironment.
Bacterium-based metabolic regulation offers a novel approach to sensitize radiotherapy and improve cancer treatment.
This biohybrid system holds potential for future clinical applications in enhancing radiotherapy effectiveness.