Lysosome-Targeted and Fluorescence-Turned "On" Cytotoxicity Induced by Alkaline Phosphatase-Triggered Self-Assembly.
Adv Healthc Mater
; 11(1): e2101346, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34624168
ABSTRACT
Selectively inducing lysosomal membrane permeabilization (LMP) is a promising strategy for cancer therapy. But integrating alkaline phosphatase (ALP)-instructed self-assembly and lysosome-targeting to induce LMP for selective killing of cancer cells was not reported. Herein, a pyrene-peptide conjugate Py-Phe-Phe-Glu-Tyr(H2 PO3 )-Gly-lyso (Py-Yp-Lyso) is rationally designed and demonstrated for its lysosome-targeting cytotoxicity on cancer cells, together with its pyrene (Py) excimer fluorescence turning "on" at 480 nm. In vitro results showed that, Py-Yp-Lyso is efficiently dephosphorylated by ALP to yield Py-Phe-Phe-Glu-Tyr-Gly-lyso (Py-Y-Lyso) which self-assembles into nanofibers. Cell experiments verified that, after being taken up by HeLa cells, the excimer fluorescence of Py-Yp-Lyso assemblies has turned "on" and the assemblies specifically target the lysosomes, inducing LMP and ultimate cancer cell death. In vivo experiments indicated that Py-Yp-Lyso has the highest inhibition effect on HeLa tumors among the four compounds studied. This is anticipated for applying Py-Yp-Lyso to treat cancers in the clinic in the future.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alkaline Phosphatase
/
Lysosomes
Limits:
Humans
Language:
En
Journal:
Adv Healthc Mater
Year:
2022
Document type:
Article
Affiliation country:
China