Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy

Dandan Jiang,1,* Mingfang Wang,1,* Tianqi Wang,1 Bo Zhang,1 Chunxi Liu,2 Na Zhang1 1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China; 2Pharmaceutical Department, Qilu Hospital of Shandong Un...

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Autores principales:	Jiang D, Wang M, Wang T, Zhang B, Liu C, Zhang N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Multifunctional Gene therapy Chemotherapy pTRAIL One-step assemble strategy CAIR theory Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/33880dc0775942ee9c82d825f78db0e7
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spelling	oai:doaj.org-article:33880dc0775942ee9c82d825f78db0e72021-12-02T07:43:45ZMultifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy1178-2013https://doaj.org/article/33880dc0775942ee9c82d825f78db0e72017-12-01T00:00:00Zhttps://www.dovepress.com/multifunctionalized-polyethyleneimine-based-nanocarriers-for-gene-and--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dandan Jiang,1,* Mingfang Wang,1,* Tianqi Wang,1 Bo Zhang,1 Chunxi Liu,2 Na Zhang1 1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China; 2Pharmaceutical Department, Qilu Hospital of Shandong University, Jinan, China *These authors contributed equally to this work Abstract: Gene therapy combined with chemotherapy to achieve synergistic therapeutic effects has been a hot topic in recent years. In this project, the human tumor necrosis factor-related apoptosis-inducing ligand-encoding plasmid gene (TRAIL) and doxorubicin (Dox)-coloaded multifunctional nanocarrier was constructed based on the theory of circulation, accumulation, internalization, and release. Briefly, polyethyleneimine (PEI) was selected as skeleton material to synthesize PEI–polyethylene glycol (PEG)–TAT (PPT). Dox was conjugated to PEI using C6-succinimidyl 6-hydrazinonicotinate acetone hydrazone (C6-SANH), and a pH-sensitive Dox-PEI (DP) conjugate was obtained. Then, intracellular cationic pH-sensitive cellular assistant PPT and DP were mixed to condense TRAIL, and TRAIL–Dox coloaded PPT/DP/TRAIL (PDT) nanocarriers were obtained by one-step assembly. TRAIL was completely condensed by DP or PPT when mass ratios (DP/PPT to TRAIL) were up to 100:64, which indicated that DP and PPT could be mixed at any ratio for TRAIL condensation. The intracellular uptake rate of PDT was enhanced (P<0.05) when the contents of PPT in PPT+DP increased from 0 to 30%. Free Dox and TRAIL-loaded nanocarriers (PPT/C6-SANH-PEI/TRAIL [PCT]) were selected as controls to verify the synergistic antitumor effects of PDT. Compared with free TRAIL, TRAIL-protein expression was upregulated by PDT and PCT on Western blotting assays. The in vitro cytotoxicity of PDT was significantly enhanced compared to free Dox and PCT (P<0.01). Furthermore, murine PDT nanocarriers showed higher in vivo antitumor ability than both the Dox group (P<0.05) and the murine PCT group (P<0.05). These results indicated that the TRAIL + Dox synergistic antitumor effect could be achieved by PDT, which paves the way to gene–drug combination therapy for cancer. Keywords: multifunctional, gene therapy, chemotherapy, TRAIL, one-step assembly strategy, CAIR theoryJiang DWang MWang TZhang BLiu CZhang NDove Medical PressarticleMultifunctionalGene therapyChemotherapypTRAILOne-step assemble strategyCAIR theoryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8681-8698 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Multifunctional Gene therapy Chemotherapy pTRAIL One-step assemble strategy CAIR theory Medicine (General) R5-920
spellingShingle	Multifunctional Gene therapy Chemotherapy pTRAIL One-step assemble strategy CAIR theory Medicine (General) R5-920 Jiang D Wang M Wang T Zhang B Liu C Zhang N Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
description	Dandan Jiang,1,* Mingfang Wang,1,* Tianqi Wang,1 Bo Zhang,1 Chunxi Liu,2 Na Zhang1 1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China; 2Pharmaceutical Department, Qilu Hospital of Shandong University, Jinan, China *These authors contributed equally to this work Abstract: Gene therapy combined with chemotherapy to achieve synergistic therapeutic effects has been a hot topic in recent years. In this project, the human tumor necrosis factor-related apoptosis-inducing ligand-encoding plasmid gene (TRAIL) and doxorubicin (Dox)-coloaded multifunctional nanocarrier was constructed based on the theory of circulation, accumulation, internalization, and release. Briefly, polyethyleneimine (PEI) was selected as skeleton material to synthesize PEI–polyethylene glycol (PEG)–TAT (PPT). Dox was conjugated to PEI using C6-succinimidyl 6-hydrazinonicotinate acetone hydrazone (C6-SANH), and a pH-sensitive Dox-PEI (DP) conjugate was obtained. Then, intracellular cationic pH-sensitive cellular assistant PPT and DP were mixed to condense TRAIL, and TRAIL–Dox coloaded PPT/DP/TRAIL (PDT) nanocarriers were obtained by one-step assembly. TRAIL was completely condensed by DP or PPT when mass ratios (DP/PPT to TRAIL) were up to 100:64, which indicated that DP and PPT could be mixed at any ratio for TRAIL condensation. The intracellular uptake rate of PDT was enhanced (P<0.05) when the contents of PPT in PPT+DP increased from 0 to 30%. Free Dox and TRAIL-loaded nanocarriers (PPT/C6-SANH-PEI/TRAIL [PCT]) were selected as controls to verify the synergistic antitumor effects of PDT. Compared with free TRAIL, TRAIL-protein expression was upregulated by PDT and PCT on Western blotting assays. The in vitro cytotoxicity of PDT was significantly enhanced compared to free Dox and PCT (P<0.01). Furthermore, murine PDT nanocarriers showed higher in vivo antitumor ability than both the Dox group (P<0.05) and the murine PCT group (P<0.05). These results indicated that the TRAIL + Dox synergistic antitumor effect could be achieved by PDT, which paves the way to gene–drug combination therapy for cancer. Keywords: multifunctional, gene therapy, chemotherapy, TRAIL, one-step assembly strategy, CAIR theory
format	article
author	Jiang D Wang M Wang T Zhang B Liu C Zhang N
author_facet	Jiang D Wang M Wang T Zhang B Liu C Zhang N
author_sort	Jiang D
title	Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
title_short	Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
title_full	Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
title_fullStr	Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
title_full_unstemmed	Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
title_sort	multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/33880dc0775942ee9c82d825f78db0e7
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_version_	1718399212101566464

Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy

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