Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

Xian Li,1,* Hao Li,2,4,* Wei Yi,3 Jianyu Chen,1 Biling Liang1 1Radiology Department, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guan...

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Autores principales:	Li X, Li H, Yi W, Chen J, Liang B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/98c6924c02f242c69e1484bca9c095c7
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spelling	oai:doaj.org-article:98c6924c02f242c69e1484bca9c095c72021-12-02T04:46:23ZAcid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells1176-91141178-2013https://doaj.org/article/98c6924c02f242c69e1484bca9c095c72013-08-01T00:00:00Zhttp://www.dovepress.com/acid-triggered-core-cross-linked-nanomicelles-for-targeted-drug-delive-a14009https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Xian Li,1,* Hao Li,2,4,* Wei Yi,3 Jianyu Chen,1 Biling Liang1 1Radiology Department, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Radiotherapy Department, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China; 4School of Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Purpose: To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods: As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results: To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors. Keywords: acid-triggered, DOX, nanomicelle carrier, folate-targeted effect, SPIONsLi XLi HYi WChen JLiang BDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 3019-3031 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li X Li H Yi W Chen J Liang B Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
description	Xian Li,1,* Hao Li,2,4,* Wei Yi,3 Jianyu Chen,1 Biling Liang1 1Radiology Department, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Radiotherapy Department, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China; 4School of Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Purpose: To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods: As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results: To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors. Keywords: acid-triggered, DOX, nanomicelle carrier, folate-targeted effect, SPIONs
format	article
author	Li X Li H Yi W Chen J Liang B
author_facet	Li X Li H Yi W Chen J Liang B
author_sort	Li X
title	Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
title_short	Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
title_full	Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
title_fullStr	Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
title_full_unstemmed	Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
title_sort	acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/98c6924c02f242c69e1484bca9c095c7
work_keys_str_mv	AT lix acidtriggeredcorecrosslinkednanomicellesfortargeteddrugdeliveryandmagneticresonanceimaginginlivercancercells AT lih acidtriggeredcorecrosslinkednanomicellesfortargeteddrugdeliveryandmagneticresonanceimaginginlivercancercells AT yiw acidtriggeredcorecrosslinkednanomicellesfortargeteddrugdeliveryandmagneticresonanceimaginginlivercancercells AT chenj acidtriggeredcorecrosslinkednanomicellesfortargeteddrugdeliveryandmagneticresonanceimaginginlivercancercells AT liangb acidtriggeredcorecrosslinkednanomicellesfortargeteddrugdeliveryandmagneticresonanceimaginginlivercancercells
_version_	1718401064576745472

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

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