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Published on: March 14, 2020
A 5-Fluorouracil-Constituted DNA Hydrogel Embedded with Quercetin Remodels Tumor Microenvironment for Robust
Yiping Li1,2,3,4, Peipei Zhao2,3,5, Junru Li2,3,5
1Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
A novel hydrogel delivers 5-fluorouracil and quercetin to combat triple-negative breast cancer (TNBC). This chemoimmunotherapy approach reduces tumor-associated macrophages and enhances anti-tumor immunity, showing promise for TNBC treatment.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunotherapy
Background:
- Triple-negative breast cancer (TNBC) treatment faces challenges from chemotherapy toxicity and immunosuppressive tumor microenvironments (TME).
- Existing chemoimmunotherapy strategies for TNBC are limited by these factors.
Purpose of the Study:
- To develop a novel injectable hydrogel (Q-5FDHG) for sustained release of 5-fluorouracil (5FU) and quercetin (Que).
- To evaluate the dual-action therapeutic efficacy of Q-5FDHG in TNBC models by modulating the TME and enhancing anti-tumor immunity.
Main Methods:
- Engineered an injectable 5-fluorouracil-constituted DNA hydrogel embedded with quercetin (Q-5FDHG) using DNA amplification.
- Administered Q-5FDHG in orthotopic murine models of TNBC.
- Assessed tumor growth, lung metastasis, and immune responses.
Main Results:
- Q-5FDHG demonstrated progressive release of 5FU and Que.
- Quercetin attenuated C-C motif chemokine ligand 2 (CCL2) secretion, reducing tumor-associated macrophage recruitment and remodeling the TME.
- 5FU inhibited tumor proliferation, induced immunogenic cell death (ICD), and enhanced tumor immunogenicity, leading to significant anti-tumor efficacy and reduced metastasis.
Conclusions:
- Q-5FDHG offers a dual-pronged strategy to overcome TNBC treatment limitations.
- This chemoimmunotherapy approach, utilizing 5FU and quercetin, shows significant potential for treating TNBC with reduced systemic toxicity and improved therapeutic outcomes.
- The study provides a promising strategy for clinical translation in TNBC therapy.
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