Dual-Targeting Dual-Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity.
Angew Chem Int Ed Engl
; 58(24): 8109-8114, 2019 06 11.
Article
em En
| MEDLINE
| ID: mdl-30945417
ABSTRACT
A novel and highly efficient dual-targeting platform was designed to ensure targeted in vivo delivery of dual-action PtIV prodrugs. The dual targeting was established by liposomal encapsulation of PtIV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug-loaded liposomes in the tumor. After the release of the PtIV prodrug inside cancer cells, a second stage of targeting directed a portion of the PtIV prodrugs to the mitochondria. Upon intracellular reduction, these PtIV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our PtIV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual-targeting dual-action platform.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Rim
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article