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Acid-assisted self-assembly of pyrene-capped tyrosine ruptures lysosomes to induce cancer cell apoptosis.
- Source :
-
RSC advances [RSC Adv] 2024 May 15; Vol. 14 (23), pp. 15840-15847. Date of Electronic Publication: 2024 May 15 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Induced lysosomal membrane permeabilization (LMP) by peptide self-assembly has emerged as an effective platform for lysosome-targeted cancer therapy. In this study, we shift this strategical paradigm and present an innovative approach to LMP induction through amino acid-based self-assembly. Pyrene-capped tyrosine (Py-Tyr), as a proof-of-concept molecule, is designed with acidity-responsive self-assembly. Under acidic conditions (pH 4), Py-Tyr is protonated with reduced charge repulsion, and self-assembles into micrometer-scaled aggregates, which exceed the biological size of lysosomes. Cell experiments showed that Py-Tyr specifically accumulates in lysosomes and induces lysosome rupture, leading to the release of cathepsin B into the cytoplasm for subsequent apoptosis activation in cancer cells. This study capitalizes on the concept of amino acid assembly for efficient LMP induction, providing a simple and versatile platform for precise and effective therapeutic interventions in cancer therapy.<br />Competing Interests: There are no conflicts to declare.<br /> (This journal is © The Royal Society of Chemistry.)
Details
- Language :
- English
- ISSN :
- 2046-2069
- Volume :
- 14
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- RSC advances
- Publication Type :
- Academic Journal
- Accession number :
- 38756853
- Full Text :
- https://doi.org/10.1039/d4ra01328j