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  • Peptide‐Driven Proton Sponge Nano‐Assembly for Imaging and Triggering Lysosome‐Regulated Immunogenic Cancer Cell Death
Title: Peptide‐Driven Proton Sponge Nano‐Assembly for Imaging and Triggering Lysosome‐Regulated Immunogenic Cancer Cell Death
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.  more » « less
Award ID(s):
1845683 2011924
PAR ID:
10501667
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Advanced Materials
ISSN:
0935-9648
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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