Dual asparagine-depriving nanoparticles against solid tumors
Abstract Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia, whereas solid tumors are unresponsive to this therapy owing to their active Asn biosynthesis. Herein, we develop a type of core-shell structured cascade-responsive nanopart...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60798-y |
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| author | Yubo Shen Huifang Wang Daoxia Guo Jiantao Liu Jinli Sun Nan Chen Haiyun Song Xiaoyuan Ji |
| author_facet | Yubo Shen Huifang Wang Daoxia Guo Jiantao Liu Jinli Sun Nan Chen Haiyun Song Xiaoyuan Ji |
| author_sort | Yubo Shen |
| collection | DOAJ |
| description | Abstract Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia, whereas solid tumors are unresponsive to this therapy owing to their active Asn biosynthesis. Herein, we develop a type of core-shell structured cascade-responsive nanoparticles (NPs) for sequential modulation of exogenous Asn supply and endogenous Asn production. The reactive oxygen species-sensitive NP shells disintegrate in the tumor microenvironment and liberate ASNase to scavenge extracellular Asn. The acid-labile NP cores subsequently decompose in the tumor cells and release rotenone to block intracellular Asn biosynthesis. Administration of the dual Asn-depriving NPs in murine models of triple-negative breast cancer and colorectal cancer substantially suppress the growth and epithelial-mesenchymal transition of primary and relapsed tumors, fully eradicate spontaneous and post-surgical metastasis, and confer long-term T cell memory for complete resistance to tumor rechallenge. This study represents a generalized strategy to harness amino acid depletion therapy against solid tumors. |
| format | Article |
| id | doaj-art-94e3f73a2b74474d9e96773d02eda4b3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-94e3f73a2b74474d9e96773d02eda4b32025-08-20T03:45:35ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-60798-yDual asparagine-depriving nanoparticles against solid tumorsYubo Shen0Huifang Wang1Daoxia Guo2Jiantao Liu3Jinli Sun4Nan Chen5Haiyun Song6Xiaoyuan Ji7School of Public Health, Shanghai Jiao Tong University School of MedicineSchool of Public Health, Shanghai Jiao Tong University School of MedicineSchool of Public Health, Shanghai Jiao Tong University School of MedicineCollege of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal UniversitySchool of Public Health, Shanghai Jiao Tong University School of MedicineCollege of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal UniversitySchool of Public Health, Shanghai Jiao Tong University School of MedicineSchool of Public Health, Shanghai Jiao Tong University School of MedicineAbstract Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia, whereas solid tumors are unresponsive to this therapy owing to their active Asn biosynthesis. Herein, we develop a type of core-shell structured cascade-responsive nanoparticles (NPs) for sequential modulation of exogenous Asn supply and endogenous Asn production. The reactive oxygen species-sensitive NP shells disintegrate in the tumor microenvironment and liberate ASNase to scavenge extracellular Asn. The acid-labile NP cores subsequently decompose in the tumor cells and release rotenone to block intracellular Asn biosynthesis. Administration of the dual Asn-depriving NPs in murine models of triple-negative breast cancer and colorectal cancer substantially suppress the growth and epithelial-mesenchymal transition of primary and relapsed tumors, fully eradicate spontaneous and post-surgical metastasis, and confer long-term T cell memory for complete resistance to tumor rechallenge. This study represents a generalized strategy to harness amino acid depletion therapy against solid tumors.https://doi.org/10.1038/s41467-025-60798-y |
| spellingShingle | Yubo Shen Huifang Wang Daoxia Guo Jiantao Liu Jinli Sun Nan Chen Haiyun Song Xiaoyuan Ji Dual asparagine-depriving nanoparticles against solid tumors Nature Communications |
| title | Dual asparagine-depriving nanoparticles against solid tumors |
| title_full | Dual asparagine-depriving nanoparticles against solid tumors |
| title_fullStr | Dual asparagine-depriving nanoparticles against solid tumors |
| title_full_unstemmed | Dual asparagine-depriving nanoparticles against solid tumors |
| title_short | Dual asparagine-depriving nanoparticles against solid tumors |
| title_sort | dual asparagine depriving nanoparticles against solid tumors |
| url | https://doi.org/10.1038/s41467-025-60798-y |
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