Attenuating Metabolic Competition of Tumor Cells for Favoring the Nutritional Demand of Immune Cells by a Branched Polymeric Drug Delivery System
Source abstract
Abstract
Abstract Tumor cells are dominant in the nutritional competition in the tumor microenvironment, and their metabolic abnormalities often lead to microenvironmental acidosis and nutrient deprivation, thereby impairing the function of immune cells and diminishing the antitumor therapeutic effect. Herein, a branched polymeric conjugate and its efficacy in attenuating the metabolic competition of tumor cells are reported. Compared with the control nanoparticles prepared from its linear counterpart, the branched‐conjugate‐based nanoparticles can more efficiently accumulate in the tumor tissue and interfere with the metabolic processes of tumor cells to increase the concentration of essential nutrients and reduce the level of immunosuppressive metabolites in the TME, thus creating a favorable environment for infiltrated immune cells. Its combined treatment with an immune checkpoint inhibitor (ICI) achieves an enhanced antitumor effect. The work presents a promising approach for targeting metabolic competition in the TME to enhance the chemo‐immunotherapeutic effect against cancers.
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Research context
OpenAlex topics: Immune cells in cancer · Autophagy in Disease and Therapy · Cancer, Hypoxia, and Metabolism
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Huaxi MR Research Center (HMRRC) Department of Radiology Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital and National Engineering Research Center for Biomaterials Sichuan University Chengdu 610041 China
Functional and molecular imaging Key Laboratory of Sichuan Province Key Laboratory of Transplant Engineering and Immunology NHC and Research Unit of Psychoradiology Chinese Academy of Medical Sciences Chengdu 610041 China
Amgen Bioprocessing Centre Keck Graduate Institute Claremont CA 91711 USA
Department of Chemical Engineering Imperial College London South Kensington Campus London SW7 2AZ UK
Department of Radiology West China Xiamen Hospital of Sichuan University Xiamen Fujian 361000 China
Funding
National Natural Science Foundation of China · West China Hospital, Sichuan University · China Postdoctoral Science Foundation
References (58)
Show source-provided references
1. 10.1126/science.aaw547310.1126/science.aaw5473 ↗
2. 10.1038/s41568-021-00378-610.1038/s41568-021-00378-6 ↗
3. 10.1038/s41577-019-0140-910.1038/s41577-019-0140-9 ↗
4. 10.1038/s41568-019-0106-z10.1038/s41568-019-0106-z ↗
5. 10.1016/j.immuni.2015.09.00110.1016/j.immuni.2015.09.001 ↗
6. 10.1038/s41568-020-0273-y10.1038/s41568-020-0273-y ↗
7. 10.1038/s41586-020-03045-210.1038/s41586-020-03045-2 ↗
8. 10.1038/s41573-019-0032-510.1038/s41573-019-0032-5 ↗
9. 10.1016/j.molcel.2020.05.03410.1016/j.molcel.2020.05.034 ↗
10. 10.1038/s41571-019-0203-710.1038/s41571-019-0203-7 ↗
11. 10.1126/science.aav258810.1126/science.aav2588 ↗
12. 10.1126/scitranslmed.abg840210.1126/scitranslmed.abg8402 ↗
13. 10.1002/adma.20210141010.1002/adma.202101410 ↗
14. 10.1002/advs.20190348310.1002/advs.201903483 ↗
15. 10.1016/j.bioactmat.2021.07.00910.1016/j.bioactmat.2021.07.009 ↗
16. 10.1038/s41573-021-00339-610.1038/s41573-021-00339-6 ↗
17. 10.1016/j.it.2021.12.00410.1016/j.it.2021.12.004 ↗
18. 10.1002/adma.20210903610.1002/adma.202109036 ↗
19. 10.1038/s41467-019-10015-410.1038/s41467-019-10015-4 ↗
20. 10.1016/j.smim.2021.10148510.1016/j.smim.2021.101485 ↗
21. 10.1039/C9CS00773C10.1039/C9CS00773C ↗
22. 10.1038/s41571-020-0413-z10.1038/s41571-020-0413-z ↗
23. 10.1021/acsnano.2c0339510.1021/acsnano.2c03395 ↗
24. 10.1002/adma.20200724710.1002/adma.202007247 ↗
25. 10.1016/j.jconrel.2021.11.02810.1016/j.jconrel.2021.11.028 ↗
26. 10.1038/s41565-022-01085-510.1038/s41565-022-01085-5 ↗
27. 10.1002/adma.20220004810.1002/adma.202200048 ↗
28. 10.1002/adma.20210459410.1002/adma.202104594 ↗
29. 10.1002/advs.20210274110.1002/advs.202102741 ↗
30. 10.1002/wnan.167010.1002/wnan.1670 ↗
31. 10.1038/s41565-019-0485-z10.1038/s41565-019-0485-z ↗
32. 10.1002/adfm.20211040810.1002/adfm.202110408 ↗
33. 10.1016/j.apsb.2021.05.00310.1016/j.apsb.2021.05.003 ↗
34. 10.1016/j.jconrel.2012.12.00910.1016/j.jconrel.2012.12.009 ↗
35. 10.1038/nrc338010.1038/nrc3380 ↗
36. 10.1038/nrd362610.1038/nrd3626 ↗
37. 10.1016/j.bioactmat.2022.08.02810.1016/j.bioactmat.2022.08.028 ↗
38. 10.1038/s41590-019-0561-410.1038/s41590-019-0561-4 ↗
39. 10.1002/1878-0261.1285110.1002/1878-0261.12851 ↗
40. 10.1038/s41590-022-01170-w10.1038/s41590-022-01170-w ↗
41. 10.1038/s41467-022-31044-610.1038/s41467-022-31044-6 ↗
42. 10.1038/s41421-019-0130-x10.1038/s41421-019-0130-x ↗
43. 10.1038/nrc325810.1038/nrc3258 ↗
44. 10.1038/s41467-021-21047-010.1038/s41467-021-21047-0 ↗
45. 10.1002/advs.20220099910.1002/advs.202200999 ↗
46. 10.1038/s41467-022-31504-z10.1038/s41467-022-31504-z ↗
47. 10.1126/sciimmunol.abn809710.1126/sciimmunol.abn8097 ↗
48. 10.1038/nature2231110.1038/nature22311 ↗
49. 10.1038/s41467-020-17046-210.1038/s41467-020-17046-2 ↗
50. 10.1016/j.cell.2015.08.01610.1016/j.cell.2015.08.016 ↗
51. 10.1126/scisignal.aao660410.1126/scisignal.aao6604 ↗
52. 10.1016/j.celrep.2019.06.01010.1016/j.celrep.2019.06.010 ↗
53. 10.1038/s41423-021-00727-310.1038/s41423-021-00727-3 ↗
54. 10.1038/s41568-019-0216-710.1038/s41568-019-0216-7 ↗
55. 10.1126/sciadv.160020010.1126/sciadv.1600200 ↗
56. 10.1016/j.devcel.2020.06.01810.1016/j.devcel.2020.06.018 ↗
57. 10.1038/s41577-019-0210-z10.1038/s41577-019-0210-z ↗
58. 10.1016/j.cell.2018.08.03910.1016/j.cell.2018.08.039 ↗