Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy

Jiajiang Xie,1,2,* Zhongxiong Fan,2,* Yang Li,2,* Yinying Zhang,2 Fei Yu,3 Guanghao Su,4 Liya Xie,5 Zhenqing Hou2 1Xiamen Xianyue Hospital, Xiamen, China; 2Research Center of Biomedical Engineering of Xiamen, Key Laboratory of Biomedical Engineering of Fujian Province, Fujian Provincial Key Laborat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xie JJ, Fan ZX, Li Y, Zhang YY, Yu F, Su GH, Xie LY, Hou ZQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	pH-sensitive prodrug self-assembly targeting combination therapy nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e16593eb53a647c994d0cabaf616abeb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e16593eb53a647c994d0cabaf616abeb
record_format	dspace
spelling	oai:doaj.org-article:e16593eb53a647c994d0cabaf616abeb2021-12-02T06:28:52ZDesign of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy1178-2013https://doaj.org/article/e16593eb53a647c994d0cabaf616abeb2018-03-01T00:00:00Zhttps://www.dovepress.com/design-of-ph-sensitive-methotrexate-prodrug-targeted-curcumin-nanopart-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiajiang Xie,1,2,* Zhongxiong Fan,2,* Yang Li,2,* Yinying Zhang,2 Fei Yu,3 Guanghao Su,4 Liya Xie,5 Zhenqing Hou2 1Xiamen Xianyue Hospital, Xiamen, China; 2Research Center of Biomedical Engineering of Xiamen, Key Laboratory of Biomedical Engineering of Fujian Province, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China; 3College of Medicals, Xiamen University, Xiamen, China; 4Children’s Hospital of Soochow University, Suzhou, China; 5The First Affiliated Hospital of Xiamen University, Xiamen, China *These authors contributed equally to this work Aim: We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. Methods: A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff’s base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). Results: The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. Conclusion: The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy. Keywords: pH-sensitive prodrug, self-assembly, targeting, combination therapy, nanoparticlesXie JJFan ZXLi YZhang YYYu FSu GHXie LYHou ZQDove Medical PressarticlepH-sensitive prodrugself-assemblytargetingcombination therapynanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1381-1398 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	pH-sensitive prodrug self-assembly targeting combination therapy nanoparticles Medicine (General) R5-920
spellingShingle	pH-sensitive prodrug self-assembly targeting combination therapy nanoparticles Medicine (General) R5-920 Xie JJ Fan ZX Li Y Zhang YY Yu F Su GH Xie LY Hou ZQ Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
description	Jiajiang Xie,1,2,* Zhongxiong Fan,2,* Yang Li,2,* Yinying Zhang,2 Fei Yu,3 Guanghao Su,4 Liya Xie,5 Zhenqing Hou2 1Xiamen Xianyue Hospital, Xiamen, China; 2Research Center of Biomedical Engineering of Xiamen, Key Laboratory of Biomedical Engineering of Fujian Province, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China; 3College of Medicals, Xiamen University, Xiamen, China; 4Children’s Hospital of Soochow University, Suzhou, China; 5The First Affiliated Hospital of Xiamen University, Xiamen, China *These authors contributed equally to this work Aim: We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. Methods: A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff’s base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). Results: The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. Conclusion: The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy. Keywords: pH-sensitive prodrug, self-assembly, targeting, combination therapy, nanoparticles
format	article
author	Xie JJ Fan ZX Li Y Zhang YY Yu F Su GH Xie LY Hou ZQ
author_facet	Xie JJ Fan ZX Li Y Zhang YY Yu F Su GH Xie LY Hou ZQ
author_sort	Xie JJ
title	Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
title_short	Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
title_full	Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
title_fullStr	Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
title_full_unstemmed	Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
title_sort	design of ph-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e16593eb53a647c994d0cabaf616abeb
work_keys_str_mv	AT xiejj designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT fanzx designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT liy designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT zhangyy designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT yuf designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT sugh designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT xiely designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy AT houzq designofphsensitivemethotrexateprodrugtargetedcurcuminnanoparticlesforefficientdualdrugdeliveryandcombinationcancertherapy
_version_	1718399905510195200

Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy

Ejemplares similares