DataVXACS NanoPaper
journal article·2025-07-08

Nanodrug Modulates Premetastatic Niche and Suppresses Metastatic Lung Adenocarcinoma via Programmed Cell Death Ligand 1 Blockade and STING Pathway Activation

Xiao Wu, Buyan Li, Haotian Liao, Xiaobo Chen, Xianzhe Yu, Jia Hu, Qing Lin, Ting Cao, Kai Xu, Qinghua Zhou, Lingling Zhu

ACS Nano· Volume 19· Issue 26
Publisher page
Source abstract

Abstract

Metastasis is a major cause of mortality in patients with lung adenocarcinoma (LUAD), with the premetastatic niche (PMN) playing a crucial role in LUAD metastasis. However, the mechanisms underlying PMN formation in LUAD remain poorly understood, hindering therapeutic advancements. Herein, we developed a PMN-targeted nanodrug by coating programmed cell death protein 1 (PD-1)-high expressed T cell membranes on the surface of STING activator 2′3′-cGAMP-loaded PLGA@MnO 2 nanoparticles (PSMP) for suppressing metastatic LUAD. Additionally, the immune profiles of PMN in LUAD were investigated using single-cell RNA-sequencing, which showed that the recruitment of programmed cell death ligand 1 (PD-L1)-high expressed myeloid-derived suppressor cells (MDSCs) drives the PMN formation in LUAD, leading to an immunosuppressive microenvironment. The in vivo results showed that the nanodrug exhibited excellent PMN-targeting capability and efficiently destroyed PMN by blocking the high expression of PD-L1 on MDSCs and activating the STING signaling pathway, thereby suppressing metastasis occurrence. Collectively, this study provides a generalizable concept that the combination of exploring characteristics of immunosuppressive PMN in LUAD and developing effective nanotherapeutics is an effective option for combating metastatic LUAD.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Immune cells in cancer · Extracellular vesicles in disease · Nanoplatforms for cancer theranostics

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

Affiliations

Lung Cancer Center/Lung Cancer Institute, West China Hospital

Sichuan University

School of Engineering

Westlake University

Department of Medical Oncology, West China Hospital

Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital

Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy

Center for Infectious Disease and Vaccine Research, West China Hospital, West China School of Medicine

Funding

West China Hospital, Sichuan University · National Key Research and Development Program of China · Science and Technology Department of Sichuan Province · National Natural Science Foundation of China · International Science and Technology Cooperation Programme · National Science and Technology Major Project · Sichuan Province Science and Technology Activities Funding for Returned Overseas Scholars

References (55)

Show source-provided references
1. 10.3322/caac.2182010.3322/caac.21820 ↗
2. 10.1038/s41419-023-05823-y10.1038/s41419-023-05823-y ↗
3. 10.1038/nrdp.2015.910.1038/nrdp.2015.9 ↗
4. 10.1038/nature2518310.1038/nature25183 ↗
5. 10.1038/nature1338510.1038/nature13385 ↗
6. 10.1038/nature1140410.1038/nature11404 ↗
7. 10.1136/bmj.n236310.1136/bmj.n2363 ↗
8. 10.1093/jnci/djv05910.1093/jnci/djv059 ↗
9. 10.1007/s13277-016-5227-310.1007/s13277-016-5227-3 ↗
10. 10.1038/s41419-020-03259-210.1038/s41419-020-03259-2 ↗
11. 10.1002/advs.20241410010.1002/advs.202414100 ↗
12. 10.1186/s12943-022-01651-410.1186/s12943-022-01651-4 ↗
13. 10.1136/jitc-2024-01000810.1136/jitc-2024-010008 ↗
14. 10.1002/smll.20240489210.1002/smll.202404892 ↗
15. 10.1016/j.bioactmat.2024.02.02610.1016/j.bioactmat.2024.02.026 ↗
16. 10.1021/acsnano.3c1303910.1021/acsnano.3c13039 ↗
17. 10.1016/j.biomaterials.2022.12173010.1016/j.biomaterials.2022.121730 ↗
18. 10.1002/smll.20210778710.1002/smll.202107787 ↗
19. 10.1002/advs.20241137810.1002/advs.202411378 ↗
20. 10.7150/ijbs.7253410.7150/ijbs.72534 ↗
21. Paget S. · Cancer Metastasis Rev. · 1989 · 8 · 98
22. 10.1158/0008-5472.CAN-06-240710.1158/0008-5472.CAN-06-2407 ↗
23. 10.1016/j.ccell.2016.07.01210.1016/j.ccell.2016.07.012 ↗
24. 10.1038/nrc.2017.610.1038/nrc.2017.6 ↗
25. 10.1016/j.ccell.2016.09.01110.1016/j.ccell.2016.09.011 ↗
26. 10.1007/s00109-015-1355-210.1007/s00109-015-1355-2 ↗
27. 10.1016/j.jconrel.2020.06.03710.1016/j.jconrel.2020.06.037 ↗
28. 10.1016/j.ccell.2023.02.01810.1016/j.ccell.2023.02.018 ↗
29. 10.1016/j.biomaterials.2020.11993210.1016/j.biomaterials.2020.119932 ↗
30. 10.1038/s41467-019-13316-w10.1038/s41467-019-13316-w ↗
31. 10.1021/acsnano.1c0602210.1021/acsnano.1c06022 ↗
32. 10.1038/s41467-021-23466-510.1038/s41467-021-23466-5 ↗
33. 10.1021/acs.nanolett.9b0049510.1021/acs.nanolett.9b00495 ↗
34. 10.1021/acs.molpharmaceut.1c0012510.1021/acs.molpharmaceut.1c00125 ↗
35. 10.1021/acs.nanolett.9b0388310.1021/acs.nanolett.9b03883 ↗
36. 10.1039/D2NR03880C10.1039/D2NR03880C ↗
37. 10.1016/j.actbio.2023.01.00910.1016/j.actbio.2023.01.009 ↗
38. 10.1038/s41467-022-30634-810.1038/s41467-022-30634-8 ↗
39. 10.1021/acsami.8b2230910.1021/acsami.8b22309 ↗
40. 10.1002/adhm.20230354310.1002/adhm.202303543 ↗
41. 10.3389/fphar.2021.68862510.3389/fphar.2021.688625 ↗
42. 10.2217/fon-2017-058510.2217/fon-2017-0585 ↗
43. 10.1038/s41586-023-05880-510.1038/s41586-023-05880-5 ↗
44. Fu X. G. · Int. J. Clin. Exp. Pathol. · 2020 · 13 · 1361
45. 10.1186/s12967-022-03649-410.1186/s12967-022-03649-4 ↗
46. 10.1021/jacs.3c0534010.1021/jacs.3c05340 ↗
47. 10.1016/j.it.2023.04.00610.1016/j.it.2023.04.006 ↗
48. 10.1038/s41565-021-00962-910.1038/s41565-021-00962-9 ↗
49. 10.1002/anie.20231450110.1002/anie.202314501 ↗
50. 10.1038/nrc262110.1038/nrc2621 ↗
51. 10.1038/s41467-020-15817-510.1038/s41467-020-15817-5 ↗
52. 10.7150/thno.8270010.7150/thno.82700 ↗
53. 10.1186/s40425-019-0770-210.1186/s40425-019-0770-2 ↗
54. 10.1038/s41598-022-14319-210.1038/s41598-022-14319-2 ↗
55. 10.1016/j.jhep.2023.08.02410.1016/j.jhep.2023.08.024 ↗