Carbon Free Radical (Râ
) Inactivates NF-κB for Radical Capping Therapy.
Angew Chem Int Ed Engl
; 63(29): e202405913, 2024 07 15.
Article
em En
| MEDLINE
| ID: mdl-38683647
ABSTRACT
Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (Râ
) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive Râ
initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of Râ
. At a temperature of 43 °C, the generated Râ
engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied Râ
micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbono
/
NF-kappa B
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2024
Tipo de documento:
Article