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Dual asparagine-depriving nanoparticles against solid tumors
Yubo Shen1, Huifang Wang1, Daoxia Guo1
1School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature Communications
|July 2, 2025
Summary
This study introduces novel nanoparticles that sequentially deplete extracellular asparagine (Asn) and block its intracellular production, effectively treating solid tumors like breast and colorectal cancer in mice.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Nanotechnology
Background:
- Solid tumors resist L-asparaginase (ASNase) therapy due to active asparagine (Asn) biosynthesis.
- Current treatments are limited for solid tumors unresponsive to traditional amino acid depletion.
Purpose of the Study:
- To develop core-shell nanoparticles for sequential modulation of exogenous Asn supply and endogenous Asn production.
- To overcome resistance of solid tumors to amino acid depletion therapy.
Main Methods:
- Designed cascade-responsive nanoparticles (NPs) with reactive oxygen species-sensitive shells and acid-labile cores.
- NPs sequentially release ASNase to scavenge extracellular Asn and rotenone to inhibit intracellular Asn biosynthesis.
- Tested NPs in murine models of triple-negative breast cancer and colorectal cancer.
Main Results:
- NPs significantly suppressed primary and relapsed tumor growth and epithelial-mesenchymal transition.
- Achieved complete eradication of spontaneous and post-surgical metastasis.
- Conferred long-term T cell memory resistance to tumor rechallenge.
Conclusions:
- This dual Asn-depriving nanoparticle strategy effectively treats solid tumors.
- Represents a generalized approach for amino acid depletion therapy against solid tumors.
- Demonstrates potential for overcoming therapeutic resistance in cancer.
