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Disulfide bonds as a molecular switch of enzyme-activatable anticancer drug precise release for fluorescence imaging and enhancing tumor therapy.
Wei, Junwu; Qian, Yangyang; Bao, Lijun; Song, Wenjie; Bi, Yunmei.
Afiliación
  • Wei J; College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China.
  • Qian Y; College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China; College of Tea (Pu'er), West Yunnan University of Applied Sciences, Pu'er, 665000, PR China.
  • Bao L; College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China.
  • Song W; College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China.
  • Bi Y; College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, PR China. Electronic address: yunmeibi@hotmail.com.
Talanta ; 278: 126394, 2024 Oct 01.
Article en En | MEDLINE | ID: mdl-38924984
ABSTRACT
Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Disulfuros / Imagen Óptica / Liberación de Fármacos Límite: Animals / Humans Idioma: En Revista: Talanta Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Disulfuros / Imagen Óptica / Liberación de Fármacos Límite: Animals / Humans Idioma: En Revista: Talanta Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos