DataVXAdvanced SciencePaper
journal article·2026-06Open access

GSH‐Responsive Nanoparticles Enhance Hepatocellular Carcinoma Immunotherapy Through Synergistic Effects of Cuproptosis and PI3K Inhibitor Combination

Lei Wu, Jintong Na, Xiyu Liu, Dongsheng Tang, Zhungang Yang, Zheng Cao, Xinyue He, Haihua Xiao, Liping Zhong, Yuan Liao, Yongxiang Zhao

Advanced Science· Volume 13· Issue 32
Publisher pageOpen full text
Source abstract

Abstract

ABSTRACT Cuproptosis, an emerging form of programmed cell death, is capable of inducing mitochondrial dysfunction. Moreover, the PI3K‐AKT‐mTOR signaling pathway contributes to tumor cell progression by reprogramming mitochondrial morphology and function. In this study, we have designed copper complex nanoparticles (NP Cu ) and PI3K‐AKT‐mTOR inhibitor Alpelisib nanoparticles (NP ALP ) that enhance the efficacy of cuproptosis‐based therapies. NP Cu triggers mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), while NP ALP inhibits the PI3K‐AKT‐mTOR signaling pathway to induce apoptosis. The combination of these two nanoparticles (NP Cu +NP ALP ) effectively activates the antitumor responses in the tumor microenvironment (TME). When combined with an anti‐programmed cell death protein 1 antibody (α‐PD‐1), NP Cu +NP ALP significantly inhibits tumor progression and activates antitumor immunity, offering a promising strategy for liver cancer treatment.
Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Cancer, Hypoxia, and Metabolism · Nanoplatforms for cancer theranostics · Ferroptosis and cancer prognosis

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

Affiliations

State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio‐targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University Nanning Guangxi P. R. China

Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University Nanning Guangxi P. R. China

Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing P. R. China

University of Chinese Academy of Sciences Beijing P. R. China

Department of Chemical and Biomolecular Engineering University of California Los Angeles California USA

References (43)

Show source-provided references
1. 10.1038/s41392-022-01229-y10.1038/s41392-022-01229-y ↗
2. 10.1038/s41568‐021‐00417‐210.1038/s41568‐021‐00417‐2 ↗
3. 10.1126/science.abf052910.1126/science.abf0529 ↗
4. 10.1038/s41423‐022‐00866‐110.1038/s41423‐022‐00866‐1 ↗
5. 10.1038/s41418‐023‐01125‐010.1038/s41418‐023‐01125‐0 ↗
6. 10.1016/j.ccr.2020.21347410.1016/j.ccr.2020.213474 ↗
7. 10.1186/s13045-022-01392-310.1186/s13045-022-01392-3 ↗
8. 10.1186/s13046‐022‐02485‐010.1186/s13046‐022‐02485‐0 ↗
9. 10.1021/acs.nanolett.3c0043410.1021/acs.nanolett.3c00434 ↗
10. 10.1038/s41571‐024‐00876‐010.1038/s41571‐024‐00876‐0 ↗
11. 10.1038/s41419-023-06264-310.1038/s41419-023-06264-3 ↗
12. 10.1038/s41419‐023‐05678‐310.1038/s41419‐023‐05678‐3 ↗
13. 10.3389/fonc.2018.0016010.3389/fonc.2018.00160 ↗
14. 10.1186/s13046-022-02437-810.1186/s13046-022-02437-8 ↗
15. 10.1073/pnas.160275111310.1073/pnas.1602751113 ↗
16. 10.1002/adma.20221226710.1002/adma.202212267 ↗
17. Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy
18. 10.1038/s41392-021-00522-610.1038/s41392-021-00522-6 ↗
19. 10.1038/s41419-021-04206-510.1038/s41419-021-04206-5 ↗
20. 10.1016/j.biopha.2022.11418310.1016/j.biopha.2022.114183 ↗
21. 10.34133/bmef.001610.34133/bmef.0016 ↗
22. 10.34133/bmef.001510.34133/bmef.0015 ↗
23. 10.34133/bmef.001210.34133/bmef.0012 ↗
24. 10.1016/j.chempr.2023.12.01910.1016/j.chempr.2023.12.019 ↗
25. 10.1002/adma.20220382010.1002/adma.202203820 ↗
26. 10.1038/s41551‐021‐00728‐710.1038/s41551‐021‐00728‐7 ↗
27. 10.1186/s12645-014-0008-410.1186/s12645-014-0008-4 ↗
28. 10.1038/s41467‐024‐50020‐w10.1038/s41467‐024‐50020‐w ↗
29. 10.1002/adma.20240681510.1002/adma.202406815 ↗
30. 10.1016/j.biopha.2024.11689210.1016/j.biopha.2024.116892 ↗
31. 10.1002/adma.20230566810.1002/adma.202305668 ↗
32. 10.1038/s41573‐024‐00920‐910.1038/s41573‐024‐00920‐9 ↗
33. 10.1038/nrc338010.1038/nrc3380 ↗
34. 10.1039/D1CS00417D10.1039/D1CS00417D ↗
35. 10.1002/adma.20231029810.1002/adma.202310298 ↗
36. 10.1038/s41392-023-01658-310.1038/s41392-023-01658-3 ↗
37. 10.1002/adma.20240311610.1002/adma.202403116 ↗
38. 10.1002/smll.20240848110.1002/smll.202408481 ↗
39. 10.1126/scitranslmed.add271210.1126/scitranslmed.add2712 ↗
40. 10.1021/jacs.3c1270610.1021/jacs.3c12706 ↗
41. 10.1038/s41467‐022‐35469‐x10.1038/s41467‐022‐35469‐x ↗
42. 10.1038/s41590‐024‐01961‐310.1038/s41590‐024‐01961‐3 ↗
43. 10.1016/j.ccell.2024.08.01310.1016/j.ccell.2024.08.013 ↗