DataVXAdvanced SciencePaper
journal article·2023-07Open access

Microfluidics‐Enabled Nanovesicle Delivers CD47/PD‐L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma

Zhenwei Su, Shaowei Dong, Yao Chen, Tuxiong Huang, Bo Qin, Qinhe Yang, Xingyu Jiang, Chang Zou

Advanced Science· Volume 10· Issue 20
Publisher pageOpen full text
Source abstract

Abstract

Abstract The CD47/PD‐L1 antibodies combination exhibits durable antitumor immunity but also elicits excessive immune‐related adverse events (IRAEs) caused by the on‐target off‐tumor immunotoxicity, hindering their clinical benefits greatly. Here, a microfluidics‐enabled nanovesicle using ultra‐pH‐sensitive polymer mannose‐poly(carboxybetaine methacrylate)‐poly(hydroxyethyl piperidine methacrylate) (Man‐PCB‐PHEP) is developed to deliver CD47/PD‐L1 antibodies (NCPA) for tumor‐acidity‐activated immunotherapy. The NCPA can specifically release antibodies in acidic environment, thereby stimulating the phagocytosis of bone marrow‐derived macrophages. In mice bearing Lewis lung carcinoma, NCPA shows significantly improved intratumoral CD47/PD‐L1 antibodies accumulation, promoted tumor‐associated macrophages remodeling to antitumoral status, and increased infiltration of dendritic cells and cytotoxic T lymphocytes, resulting in more favorable treatment effect compared to those of free antibodies. Additionally, NCPA also shows less IRAEs, including anemia, pneumonia, hepatitis, and small intestinal inflammation in vivo. Altogether, a potent dual checkpoint blockade immunotherapy utilizing NCPA with enhanced antitumor immunity and reduced IRAEs is demonstrated.
Source: crossref · Quality: baseline

Research context

PolymersNanomaterials

OpenAlex topics: Phagocytosis and Immune Regulation · Nanoplatforms for cancer theranostics · Extracellular vesicles in disease

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

Affiliations

Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases Department of Clinical Medical Research Center The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology Shenzhen People’s Hospital Shenzhen Guangdong 518001 P. R. China

Guangdong Provincial Key Laboratory of Advanced Biomaterials Shenzhen Key Laboratory of Smart Healthcare Engineering Department of Biomedical Engineering Southern University of Science and Technology No. 1088 Xueyuan Rd, Nanshan District Shenzhen Guangdong 518055 P. R. China

School of Medicine Life and Health Sciences The Chinese University of Hong Kong (Shenzhen) 2001 Longxiang Road Shenzhen Guangdong 518172 P. R. China

Department of Hematology and Oncology Shenzhen Children's Hospital 7019 Yitian Road Shenzhen Guangdong 518038 P. R. China

Department of Pharmacology and International Cancer Center Shenzhen University Shenzhen Guangdong 518060 P. R. China

Aier School of Ophthalmology Central South University Changsha Hunan 410083 P. R. China

School of Traditional Chinese Medicine Jinan University Guangzhou Guangdong 510632 P. R. China

References (49)

Show source-provided references
1. 10.1126/science.aar406010.1126/science.aar4060 ↗
2. 10.1126/science.aax018210.1126/science.aax0182 ↗
3. 10.1016/j.immuni.2018.03.00710.1016/j.immuni.2018.03.007 ↗
4. 10.1038/s41573-021-00155-y10.1038/s41573-021-00155-y ↗
5. 10.1038/d41573-020-00204-y10.1038/d41573-020-00204-y ↗
6. 10.3389/fimmu.2020.0001810.3389/fimmu.2020.00018 ↗
7. 10.1200/JCO.2020.38.5_suppl.1810.1200/JCO.2020.38.5_suppl.18 ↗
8. Z.Yang Y.Peng W.Guo J.Xu L.Li H.Tian R.Li L.Liu F.Tan S.Gao J.He 2021 12 1743.10.3389/fimmu.2021.788985 ↗
9. 10.1016/j.ejca.2017.02.01310.1016/j.ejca.2017.02.013 ↗
10. 10.1172/jci.insight.13472810.1172/jci.insight.134728 ↗
11. 10.1016/j.it.2017.12.00510.1016/j.it.2017.12.005 ↗
12. 10.1016/j.celrep.2018.07.06210.1016/j.celrep.2018.07.062 ↗
13. 10.1016/j.ebiom.2019.03.01810.1016/j.ebiom.2019.03.018 ↗
14. 10.1073/pnas.160426811310.1073/pnas.1604268113 ↗
15. 10.1016/j.cell.2021.02.01110.1016/j.cell.2021.02.011 ↗
16. 10.1056/NEJMra170348110.1056/NEJMra1703481 ↗
17. 10.1016/j.cell.2021.09.02010.1016/j.cell.2021.09.020 ↗
18. 10.1016/S1470-2045(20)30107-810.1016/S1470-2045(20)30107-8 ↗
19. 10.1038/s43018-022-00401-110.1038/s43018-022-00401-1 ↗
20. 10.7326/M17-207310.7326/M17-2073 ↗
21. 10.1038/s41551-021-00803-z10.1038/s41551-021-00803-z ↗
22. 10.1126/sciadv.abg729110.1126/sciadv.abg7291 ↗
23. 10.1021/acsami.0c2042210.1021/acsami.0c20422 ↗
24. 10.1002/smll.20190683210.1002/smll.201906832 ↗
25. 10.1016/j.biomaterials.2020.12063610.1016/j.biomaterials.2020.120636 ↗
26. 10.1016/j.biomaterials.2020.12040710.1016/j.biomaterials.2020.120407 ↗
27. 10.1016/j.biomaterials.2019.11935810.1016/j.biomaterials.2019.119358 ↗
28. 10.1186/s40425-019-0586-010.1186/s40425-019-0586-0 ↗
29. 10.1080/1061186X.2019.166904310.1080/1061186X.2019.1669043 ↗
30. 10.1186/s12929-019-0592-z10.1186/s12929-019-0592-z ↗
31. 10.1002/anie.20150009610.1002/anie.201500096 ↗
32. 10.1126/sciadv.aay795210.1126/sciadv.aay7952 ↗
33. 10.1021/acs.nanolett.0c0405310.1021/acs.nanolett.0c04053 ↗
34. 10.1126/sciadv.abe785310.1126/sciadv.abe7853 ↗
35. 10.1126/sciadv.aba102810.1126/sciadv.aba1028 ↗
36. 10.1021/cs400684x10.1021/cs400684x ↗
37. 10.1002/jps.2205410.1002/jps.22054 ↗
38. 10.1016/j.ijbiomac.2006.03.02310.1016/j.ijbiomac.2006.03.023 ↗
39. 10.1038/s41587-019-0135-x10.1038/s41587-019-0135-x ↗
40. 10.1172/JCI12339110.1172/JCI123391 ↗
41. 10.1038/s41467-021-24767-510.1038/s41467-021-24767-5 ↗
42. 10.4155/ppa-2020-001710.4155/ppa-2020-0017 ↗
43. 10.1126/sciadv.aax316010.1126/sciadv.aax3160 ↗
44. Mi Y. · Adv. Mater. · 2018 · 30
45. 10.1038/s41568-019-0186-910.1038/s41568-019-0186-9 ↗
46. 10.1021/acs.accounts.0c0033910.1021/acs.accounts.0c00339 ↗
47. 10.1038/s41573-018-0006-z10.1038/s41573-018-0006-z ↗
48. 10.1002/adma.20200618910.1002/adma.202006189 ↗
49. 10.1021/acs.nanolett.9b0058410.1021/acs.nanolett.9b00584 ↗