journal article·2024-03-04

Metal-Free Nanocomposites with Endogenous Labile Iron Pool Disturbing Capacity for Tumor Therapy through Synergetic Stock Depletion and Supply Blockage Strategy

Sheng Zhao, Ziqun Chen, Jingjing Wang, Chunmei Chen, Yi Ouyang, Mengyuan Wu, Qun Zhang, Yang Cao, Hui Liu

ACS Materials Letters· Volume 6· Issue 3
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Abstract

Metal iron plays exceedingly important roles in maintaining normal biological activities and is stored as an intracellular labile iron pool (LIP). Disturbing LIP balance to disorganize physiological reactions holds great promise in tumor therapy yet is still lacking exploration. Herein, a novel synergetic strategy was designed for tumor therapy with high efficacy and biocompatibility, which was realized through the metal-free poly(lactic- co -glycolic acid) (PLGA)-ethylenediaminetetraacetic acid (EDTA)-ebselen (EBS) nanocomposites. After degradation, EDTA chelates Fe 2+ to deplete intracellular LIP, and EBS inactivates DMT1 protein to inhibit iron supplementation from extracellular regions. This LIP destruction causes the downregulation of iron–sulfur cluster levels, which compromises mitochondrial energy metabolism and arrests the cell cycle. Effective tumor elimination is achieved under PLGA-EDTA-EBS treatment with negligible side effects. This work presents an effective formulation for tumor therapy through a synergetic stock depletion and supply blockage strategy, thereby providing essential implications for the design of tumor therapeutic methods with minimal biosafety issues.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Metalloenzymes and iron-sulfur proteins · Trace Elements in Health · Nanocluster Synthesis and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China

Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China

Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China

Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China

Funding

Natural Science Foundation of Chongqing Municipality · Senior Medical Talents Program of Chongqing for Young and Middle-aged · Basic and Applied Basic Research Project of Guangzhou Basic Research Program

References (53)

Show source-provided references
1. 10.3389/fcell.2022.86483010.3389/fcell.2022.864830 ↗
2. 10.1021/cr400466510.1021/cr4004665 ↗
3. 10.1186/s12929-017-0394-010.1186/s12929-017-0394-0 ↗
4. 10.1080/0889311X.2010.48561610.1080/0889311X.2010.485616 ↗
5. 10.1021/acsnano.1c0545110.1021/acsnano.1c05451 ↗
6. 10.1039/D1SC00929J10.1039/D1SC00929J ↗
7. 10.1038/s41568-021-00417-210.1038/s41568-021-00417-2 ↗
8. 10.3390/nu408087510.3390/nu4080875 ↗
9. 10.1016/S0891-5849(02)01006-710.1016/S0891-5849(02)01006-7 ↗
10. 10.1093/brain/awz07210.1093/brain/awz072 ↗
11. 10.3390/cells912259110.3390/cells9122591 ↗
12. 10.1021/jacs.0c0560410.1021/jacs.0c05604 ↗
13. 10.1016/j.mrfmmm.2003.08.00410.1016/j.mrfmmm.2003.08.004 ↗
14. 10.1007/s10534-011-9476-810.1007/s10534-011-9476-8 ↗
15. 10.1074/jbc.R117.78710110.1074/jbc.R117.787101 ↗
16. 10.1038/nature1187110.1038/nature11871 ↗
17. 10.1146/annurev.biochem.75.103004.14253910.1146/annurev.biochem.75.103004.142539 ↗
18. 10.1126/science.277.5326.65310.1126/science.277.5326.653 ↗
19. 10.1039/C7MT00116A10.1039/C7MT00116A ↗
20. 10.3390/antiox1009145810.3390/antiox10091458 ↗
21. 10.1016/S1570-9639(04)00054-810.1016/S1570-9639(04)00054-8 ↗
22. 10.1016/j.gendis.2022.11.02210.1016/j.gendis.2022.11.022 ↗
23. 10.1002/ejic.20210095310.1002/ejic.202100953 ↗
24. 10.1016/j.molcel.2011.09.02110.1016/j.molcel.2011.09.021 ↗
25. 10.1021/jacsau.1c0007810.1021/jacsau.1c00078 ↗
26. 10.1038/nrc349510.1038/nrc3495 ↗
27. 10.1021/jacs.2c0397310.1021/jacs.2c03973 ↗
28. 10.18632/aging.20351210.18632/aging.203512 ↗
29. 10.1023/A:102070221309910.1023/A:1020702213099 ↗
30. 10.1039/C8MT00048D10.1039/C8MT00048D ↗
31. 10.1523/JNEUROSCI.3262-17.201810.1523/JNEUROSCI.3262-17.2018 ↗
32. 10.1016/j.cej.2018.07.07810.1016/j.cej.2018.07.078 ↗
33. 10.1021/acsami.9b1185010.1021/acsami.9b11850 ↗
34. 10.1016/j.chemosphere.2022.13591710.1016/j.chemosphere.2022.135917 ↗
35. 10.1016/j.watres.2019.11495710.1016/j.watres.2019.114957 ↗
36. 10.1002/chem.20200015910.1002/chem.202000159 ↗
37. 10.1016/j.neuint.2012.05.01610.1016/j.neuint.2012.05.016 ↗
38. 10.1155/2021/980079410.1155/2021/9800794 ↗
39. 10.1021/acsami.2c1443610.1021/acsami.2c14436 ↗
40. 10.1002/adhm.20230033810.1002/adhm.202300338 ↗
41. 10.1002/anie.20210174410.1002/anie.202101744 ↗
42. 10.1002/adhm.20220336210.1002/adhm.202203362 ↗
43. 10.1021/acsnano.2c0515210.1021/acsnano.2c05152 ↗
44. 10.1016/j.etap.2019.10322010.1016/j.etap.2019.103220 ↗
45. 10.1007/s12011-016-0759-310.1007/s12011-016-0759-3 ↗
46. 10.1016/j.brainres.2015.02.00610.1016/j.brainres.2015.02.006 ↗
47. 10.1016/j.jconrel.2012.01.04310.1016/j.jconrel.2012.01.043 ↗
48. 10.1016/j.actbio.2013.12.03310.1016/j.actbio.2013.12.033 ↗
49. 10.1038/ncomms1296710.1038/ncomms12967 ↗
50. 10.1016/j.chempr.2020.06.01310.1016/j.chempr.2020.06.013 ↗
51. 10.1038/s41587-020-0707-910.1038/s41587-020-0707-9 ↗
52. 10.1021/acs.nanolett.2c0502910.1021/acs.nanolett.2c05029 ↗
53. 10.1016/j.molstruc.2022.13318010.1016/j.molstruc.2022.133180 ↗