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Related Experiment Video

Updated: Jul 10, 2026

Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

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Multiplex Methionine Modulating Hydrogel for Cancer Metabolic Therapy.

Siyu Ma¹, Wen Zhu¹, Xiaoyuan Ji¹

¹School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Advanced Materials (Deerfield Beach, Fla.)

|May 16, 2025

Summary

This study developed a novel hydrogel therapy to block methionine metabolism in tumor cells, effectively inhibiting cancer growth and enhancing immune responses. This localized approach offers a promising new strategy for amino acid starvation-based cancer treatments.

Keywords:

S‐adenosyl methionine cancer metabolic therapy hydrogel nanoparticle triple methionine modulation

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Area of Science:

Oncology
Biomedical Engineering
Cancer Therapeutics

Background:

Tumor cells exhibit high dependence on methionine, making it a potential therapeutic target.
Systemic methionine restriction can cause side effects due to methionine's essential metabolic roles.

Purpose of the Study:

To develop a localized drug delivery system for multilayered methionine blockade within tumors.
To investigate the therapeutic efficacy of a novel hydrogel in preclinical cancer models.

Main Methods:

Encapsulation of small molecule inhibitors (PF9366, adenosine dialdehyde) and JPH203 into tumor-targeting nanoparticles (NPs).
Co-loading of NPs into a reactive oxygen species-sensitive hydrogel to form the multiplex methionine modulating hydrogel (3 M Gel).
Evaluation of 3 M Gel efficacy in murine models of triple-negative breast cancer, hepatocellular carcinoma, and colorectal cancer.

Main Results:

3 M Gel effectively restricted S-adenosyl methionine generation and histone methylation in tumors.
The treatment stimulated immunogenic cell death and potent immune responses, restraining tumor progression.
3 M Gel remodeled the tumor microenvironment, overcoming immune checkpoint blockade resistance in triple-negative breast cancer.

Conclusions:

The developed 3 M Gel provides a localized triple regulation strategy for methionine metabolism.
This approach offers a novel pathway for amino acid starvation-based cancer therapy with enhanced efficacy and reduced systemic side effects.