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Related Experiment Video

Updated: May 22, 2025

Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models
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Carbon Dot-Linked Hydrogel for TAMs Transform: Spatiotemporal Manipulation to Reshape Tumor Microenvironment.

Lingyun Li1, Jun Wu1, Xue Wu1

  • 1Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Taipa, Macau SAR, 999078, P. R. China.

Advanced Materials (Deerfield Beach, Fla.)
|April 4, 2025
PubMed
Summary

This study introduces a novel hydrogel that guides and reprograms tumor-associated macrophages (TAMs) to enhance antitumor immunity. The TAMs Transform Factory (TTF-L-C) platform effectively boosts T cell activation for improved cancer immunotherapy.

Keywords:
carbon dotshydrogelmacrophage recruitmentmacrophage reprogramtumor immunotherapy

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Materials Science

Background:

  • Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME) and crucial targets for cancer immunotherapy.
  • Effective manipulation of TAMs is vital for enhancing antitumor immunity and overcoming immune suppression within the TME.

Purpose of the Study:

  • To develop an injectable hydrogel system, TAMs Transform Factory (TTF-L-C), for spatiotemporal manipulation of TAMs.
  • To investigate the capacity of TTF-L-C to recruit, reprogram, and activate macrophages for improved cancer immunotherapy.

Main Methods:

  • Fabrication of carbon dots (CDs)-linked egg white hydrogel (TTF-L-C) for macrophage recruitment and reprogramming.
  • Utilizing CDs for directional macrophage recruitment via Ctnnd1 upregulation.
  • In situ reprogramming of macrophages and blockade of PD-L1 within the hydrogel.
  • Assessment of TTF-L-C efficacy in promoting M1 macrophage release, dendritic cell maturation, and T cell activation.

Main Results:

  • The fabricated CDs significantly promoted macrophage migration and spatial enrichment.
  • TTF-L-C successfully reprogrammed recruited macrophages and blocked PD-L1.
  • The system facilitated the release of immune-activated M1 macrophages, promoted dendritic cell maturation, and boosted T cell activation.
  • Peritumoral injection of TTF-L-C demonstrated enhanced tumor immunotherapy in vivo with good biosafety.

Conclusions:

  • TTF-L-C serves as a safe and effective platform for multi-stage regulation of TAMs at spatial, cellular, and molecular levels.
  • This approach reshapes the tumor microenvironment from suppressive to immune-activating.
  • TTF-L-C shows significant potential for enhancing cancer immunotherapy and various other biomedical applications.