DataVXAdvanced MaterialsPaper
journal article·2024-05Open access

Peptide‐Driven Proton Sponge Nano‐Assembly for Imaging and Triggering Lysosome‐Regulated Immunogenic Cancer Cell Death

Tengyu He, Jing Wen, Wenjian Wang, Zeliang Hu, Chuxuan Ling, Zhongchao Zhao, Yong Cheng, Yu‐Ci Chang, Ming Xu, Zhicheng Jin, Lubna Amer, Lekshmi Sasi, Lei Fu, Nicole F. Steinmetz, Tariq M. Rana, Peng Wu, Jesse V. Jokerst

Advanced Materials· Volume 36· Issue 19
Publisher pageOpen full text
Source abstract

Abstract

Abstract Triggering lysosome‐regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an “immune‐cold” tumor “hot”—a key challenge faced by cancer immunotherapies. Proton sponge such as high‐molecular‐weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano‐assemblies (PSNAs) with self‐assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low‐molecular‐weight branched PEI covalently bound to self‐assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation‐induced emission‐based luminogen). Assembly of PEI assisted by the self‐assembling peptide‐PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self‐assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing‐regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA‐triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.
Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Toxoplasma gondii Research Studies · Antimicrobial Peptides and Activities

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

Affiliations

Program in Materials Science and Engineering University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Division of Genetics, Program in Immunology Bioinformatics and Systems Biology Program Institute for Genomic Medicine, Department of Pediatrics University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Department of Molecular & Cellular Biology The Scripps Research Institute La Jolla CA 92037 USA

Department of Chemistry and Biochemistry University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Department of NanoEngineering University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Department of NanoEngineering Department of Bioengineering, Department of Radiology Center for Nano‐ImmunoEngineering Institute for Materials Discovery and Design Moores Cancer Center Center for Engineering in Cancer Institute of Engineering in Medicine Shu and K. C. Chien and Peter Farrell Collaboratory University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Program in Materials Science and Engineering, and Department of Radiology Department of NanoEngineering University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA

Funding

National Institutes of Health · National Science Foundation

References (51)

Show source-provided references
1. 10.1016/j.it.2022.04.01010.1016/j.it.2022.04.010 ↗
2. 10.1002/anie.20201028110.1002/anie.202010281 ↗
3. 10.1021/jacs.3c0123110.1021/jacs.3c01231 ↗
4. 10.1016/j.matt.2022.08.02610.1016/j.matt.2022.08.026 ↗
5. 10.1002/adma.20200851810.1002/adma.202008518 ↗
6. 10.3389/fimmu.2019.0016810.3389/fimmu.2019.00168 ↗
7. 10.1186/s13046-021-01959-x10.1186/s13046-021-01959-x ↗
8. 10.1016/j.apsb.2020.01.00710.1016/j.apsb.2020.01.007 ↗
9. 10.1002/1878-0261.1285110.1002/1878-0261.12851 ↗
10. 10.1038/s41577-019-0210-z10.1038/s41577-019-0210-z ↗
11. 10.1074/jbc.M111.23851910.1074/jbc.M111.238519 ↗
12. 10.1016/j.nantod.2020.10106110.1016/j.nantod.2020.101061 ↗
13. 10.3389/fimmu.2022.87445910.3389/fimmu.2022.874459 ↗
14. 10.1016/j.biomaterials.2016.03.00310.1016/j.biomaterials.2016.03.003 ↗
15. 10.3390/cancers1406154610.3390/cancers14061546 ↗
16. 10.1016/j.jconrel.2017.11.05010.1016/j.jconrel.2017.11.050 ↗
17. 10.1002/adma.20190405810.1002/adma.201904058 ↗
18. 10.1039/c4tb00056k10.1039/c4tb00056k ↗
19. 10.1038/s41565-022-01125-010.1038/s41565-022-01125-0 ↗
20. 10.1021/acs.nanolett.9b0324510.1021/acs.nanolett.9b03245 ↗
21. 10.1038/nmat239810.1038/nmat2398 ↗
22. 10.1002/advs.20150022310.1002/advs.201500223 ↗
23. 10.1038/s41578-021-00328-610.1038/s41578-021-00328-6 ↗
24. 10.1039/D0BM01313G10.1039/D0BM01313G ↗
25. 10.1021/acs.chemmater.2c0085710.1021/acs.chemmater.2c00857 ↗
26. 10.1021/acsanm.1c0028510.1021/acsanm.1c00285 ↗
27. Burgess D. J. · Nat. Rev. Cancer · 2012 · 12 · 737
28. 10.1002/anbr.20220010110.1002/anbr.202200101 ↗
29. 10.1038/s41401-019-0281-110.1038/s41401-019-0281-1 ↗
30. 10.2147/IJN.S32134310.2147/IJN.S321343 ↗
31. 10.1038/s41419-020-03032-510.1038/s41419-020-03032-5 ↗
32. 10.1016/j.apsb.2020.07.00310.1016/j.apsb.2020.07.003 ↗
33. 10.1111/nyas.1295310.1111/nyas.12953 ↗
34. 10.1021/jacs.2c1322210.1021/jacs.2c13222 ↗
35. 10.1021/acsnano.8b0515110.1021/acsnano.8b05151 ↗
36. 10.1038/mt.2012.18510.1038/mt.2012.185 ↗
37. 10.1021/acs.chemmater.2c0085710.1021/acs.chemmater.2c00857 ↗
38. 10.1021/acs.analchem.2c0498810.1021/acs.analchem.2c04988 ↗
39. 10.1046/j.1432-1327.1998.2570293.x10.1046/j.1432-1327.1998.2570293.x ↗
40. 10.1002/anie.20221439410.1002/anie.202214394 ↗
41. 10.1093/protein/gzt02310.1093/protein/gzt023 ↗
42. 10.1021/nn200546k10.1021/nn200546k ↗
43. 10.1002/advs.20220279710.1002/advs.202202797 ↗
44. 10.1158/1078-0432.CCR-20-283310.1158/1078-0432.CCR-20-2833 ↗
45. 10.1007/s10495-018-1502-710.1007/s10495-018-1502-7 ↗
46. 10.1021/acsnano.2c0321910.1021/acsnano.2c03219 ↗
47. 10.1152/ajpcell.00462.201010.1152/ajpcell.00462.2010 ↗
48. Kafil V. · Bioimpacts · 2011 · 1 · 23
49. 10.1016/j.tsf.2015.09.04710.1016/j.tsf.2015.09.047 ↗
50. 10.1073/pnas.160588811310.1073/pnas.1605888113 ↗
51. 10.1073/pnas.030834510110.1073/pnas.0308345101 ↗