- Title
- Peptide-Conjugated Micelles Make Effective Mimics of the TRAIL Protein for Driving Apoptosis in Colon Cancer
- Creator
- Han, Zifei; Li, Zihao; Raveendran, Radhika; Farazi, Shegufta; Cao, Cheng; Chapman, Robert; Stenzel, Martina H.
- Relation
- Biomacromolecules Vol. 24, Issue 11, p. 5046-5057
- Publisher Link
- http://dx.doi.org/10.1021/acs.biomac.3c00668
- Publisher
- American Chemical Society (ACS)
- Resource Type
- journal article
- Date
- 2023
- Description
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) drives apoptosis selectively in cancer cells by clustering death receptors (DR4 and DR5). While it has excellent in vitro selectivity and toxicity, the TRAIL protein has a very low circulation half-life in vivo, which has hampered clinical development. Here, we developed core-cross-linked micelles that present multiple copies of a TRAIL-mimicking peptide at its surface. These micelles successfully induce apoptosis in a colon cancer cell line (COLO205) via DR4/5 clustering. Micelles with a peptide density of 15% (roughly 1 peptide/45 nm2) displayed the strongest activity with an IC50 value of 0.8 μM (relative to peptide), demonstrating that the precise spatial arrangement of ligands imparted by a protein such as a TRAIL may not be necessary for DR4/5/signaling and that a statistical network of monomeric ligands may suffice. As micelles have long circulation half-lives, we propose that this could provide a potential alternative drug to TRAIL and stimulate the use of micelles in other membrane receptor clustering networks.
- Subject
- apoptosis; micelles; peptides and proteins; polymers; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1499615
- Identifier
- uon:54743
- Identifier
- ISSN:1525-7797
- Language
- eng
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