Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery

Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery

Qing Zhou,1,* Tiehong Yang,1,* Youbei Qiao,1 Songyan Guo,1 Lin Zhu,2 Hong Wu11Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Ph...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Zhou Q, Yang T, Qiao Y, Guo S, Zhu L, Wu H
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/58c603ac30c14fe7b2732cb0c622bff0
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:58c603ac30c14fe7b2732cb0c622bff0
record_format dspace
spelling oai:doaj.org-article:58c603ac30c14fe7b2732cb0c622bff02021-12-02T01:32:09ZPreparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery1178-2013https://doaj.org/article/58c603ac30c14fe7b2732cb0c622bff02015-03-01T00:00:00Zhttp://www.dovepress.com/preparation-of-polybeta-l-malic-acid-based-charge-conversional-nanocon-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Qing Zhou,1,* Tiehong Yang,1,* Youbei Qiao,1 Songyan Guo,1 Lin Zhu,2 Hong Wu11Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, Texas, USA*These authors contributed equally to this workAbstract: In this study, a multifunctional poly(β-L-malic acid)-based nanoconjugate with a pH-dependent charge conversional characteristic was developed for tumor-specific drug delivery. The short branched polyethylenimine-modified poly(β-L-malic acid) (PEPM) was first synthesized. Then, the fragment HAb18 F(ab′)2 and 2,3-dimethylmaleic anhydride were covalently attached to the PEPM to form the nanoconjugate, HDPEPM. In this nanoconjugate, the 2,3-dimethylmaleic anhydride, the shielding group, could shield the positive charge of the conjugate at pH 7.4, while it was selectively hydrolyzed in the tumor extracellular space (pH 6.8) to expose the previously-shielded positive charge. To study the anticancer activity, the anticancer drug, doxorubicin, was covalently attached to the nanoconjugate. The doxorubicin-loaded HDPEPM nanoconjugate was able to efficiently undergo a quick charge conversion from -11.62 mV to 9.04 mV in response to the tumor extracellular pH. The electrostatic interaction between the positively charged HDPEPM nanoconjugates and the negatively charged cell membrane significantly enhanced their cellular uptake, resulting in the enhanced anticancer activity. Also, the tumor targetability of the nanoconjugates could be further improved via the fragment HAb18 F(ab′)2 ligand–receptor-mediated tumor cell-specific endocytosis.Keywords: nanoconjugate, charge-conversional, PMLA, pH-sensitive  Zhou QYang TQiao YGuo SZhu LWu HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1941-1952 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Zhou Q
Yang T
Qiao Y
Guo S
Zhu L
Wu H
Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
description Qing Zhou,1,* Tiehong Yang,1,* Youbei Qiao,1 Songyan Guo,1 Lin Zhu,2 Hong Wu11Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, Texas, USA*These authors contributed equally to this workAbstract: In this study, a multifunctional poly(β-L-malic acid)-based nanoconjugate with a pH-dependent charge conversional characteristic was developed for tumor-specific drug delivery. The short branched polyethylenimine-modified poly(β-L-malic acid) (PEPM) was first synthesized. Then, the fragment HAb18 F(ab′)2 and 2,3-dimethylmaleic anhydride were covalently attached to the PEPM to form the nanoconjugate, HDPEPM. In this nanoconjugate, the 2,3-dimethylmaleic anhydride, the shielding group, could shield the positive charge of the conjugate at pH 7.4, while it was selectively hydrolyzed in the tumor extracellular space (pH 6.8) to expose the previously-shielded positive charge. To study the anticancer activity, the anticancer drug, doxorubicin, was covalently attached to the nanoconjugate. The doxorubicin-loaded HDPEPM nanoconjugate was able to efficiently undergo a quick charge conversion from -11.62 mV to 9.04 mV in response to the tumor extracellular pH. The electrostatic interaction between the positively charged HDPEPM nanoconjugates and the negatively charged cell membrane significantly enhanced their cellular uptake, resulting in the enhanced anticancer activity. Also, the tumor targetability of the nanoconjugates could be further improved via the fragment HAb18 F(ab′)2 ligand–receptor-mediated tumor cell-specific endocytosis.Keywords: nanoconjugate, charge-conversional, PMLA, pH-sensitive  
format article
author Zhou Q
Yang T
Qiao Y
Guo S
Zhu L
Wu H
author_facet Zhou Q
Yang T
Qiao Y
Guo S
Zhu L
Wu H
author_sort Zhou Q
title Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
title_short Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
title_full Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
title_fullStr Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
title_full_unstemmed Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
title_sort preparation of poly(β-l-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/58c603ac30c14fe7b2732cb0c622bff0
work_keys_str_mv AT zhouq preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
AT yangt preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
AT qiaoy preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
AT guos preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
AT zhul preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
AT wuh preparationofpolybetalmalicacidbasedchargeconversionalnanoconjugatesfortumorspecificuptakeandcellulardelivery
_version_ 1718403015407304704

Ejemplares similares