Nuclear-targeted chimeric peptide nanorods to amplify innate anti-tumor immunity through localized DNA damage and STING activation.
J Control Release
; 369: 531-544, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38580138
ABSTRACT
Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ, and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Inmunidad Innata
/
Proteínas de la Membrana
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article