Implantable hydrogel embedded dark-gold nanoswitch as a theranostic probe to sense and overcome cancer multidrug resistance.
Proc Natl Acad Sci U S A
; 112(11): E1278-87, 2015 Mar 17.
Article
em En
| MEDLINE
| ID: mdl-25733851
ABSTRACT
Multidrug resistance (MDR) in cancer cells is a substantial limitation to the success of chemotherapy. Here, we describe facile means to overcome resistance by silencing the multidrug resistance protein 1 (MRP1), before chemotherapeutic drug delivery in vivo with a single local application. Our platform contains hydrogel embedded with dark-gold nanoparticles modified with 5-fluorouracil (5-FU)-intercalated nanobeacons that serve as an ON/OFF molecular nanoswitch triggered by the increased MRP1 expression within the tumor tissue microenvironment. This nanoswitch can sense and overcome MDR prior to local drug release. The nanobeacons comprise a 5-FU intercalated DNA hairpin, which is labeled with a near-infrared (NIR) dye and a dark-quencher. The nanobeacons are designed to open and release the intercalated drug only upon hybridization of the DNA hairpin to a complementary target, an event that restores fluorescence emission due to nanobeacons conformational reorganization. Despite the cross-resistance to 5-FU, more than 90% tumor reduction is achieved in vivo in a triple-negative breast cancer model following 80% MRP1 silencing compared with the continuous tumor growth following only drug or nanobeacon administration. Our approach can be applied to reverse cross-resistance to other chemotherapeutic drugs and restore treatment efficacy. As a universal nanotheranostic probe, this platform can pave the way to early cancer detection and treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
/
Implantes Experimentais
/
Hidrogel de Polietilenoglicol-Dimetacrilato
/
Nanopartículas
/
Ouro
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article