NF-κB hijacking theranostic Pt(ll) complex in cancer therapy.
Theranostics
; 9(8): 2158-2166, 2019.
Article
en En
| MEDLINE
| ID: mdl-31149035
ABSTRACT
Platinum complexes have been used for anti-cancer propose for decades, however, their high side effects resulting from damage to healthy cells cannot be neglected and prevent further clinical utilisation. Here, we designed a cyclometalated platinum (II) complex that can bind the endogenous nuclear factor-κB (NF-κB) protein. Employing detailed colocalization studies in co-culture cell line models, we show that by binding to NF-κB, the platinum (II) complex is capable of upregulated nuclear translocation specifically in cancer but not normal cells, thereby impairing cancer proliferation without disturbing healthy cells. In a murine tumour model, the platinum (II) complex prevents tumour growth to a greater extent than cisplatin and with considerably lower side-effects and kidney damage. Considering its weak damage to normal cells combined with high toxicity to cancer cells, this NF-κB-binding platinum complex is a potential anti-cancer candidate and acts to verify the strategy of hijacking endogenous trans-nuclear proteins to achieve cancer-cell specificity and enhance therapeutic indices.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Platino
/
Subunidad p50 de NF-kappa B
/
Nanomedicina Teranóstica
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Theranostics
Año:
2019
Tipo del documento:
Article