A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery

Peng Li, Donghua Liu, Lei Miao, Chunxi Liu, Xiaoli Sun, Yongjun Liu, Na ZhangSchool of Pharmaceutical Science, Shandong University, Jinan, Shandong, People&rsquo;s Republic of ChinaBackground: The success of gene therapy asks for the development of multifunctional vectors that could overcome...

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Autores principales:	Li P, Liu DH, Miao L, Liu CX, Sun XL, Liu YJ, Zhang N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/34c95ebaafa74950afdaf49b11118e42
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spelling	oai:doaj.org-article:34c95ebaafa74950afdaf49b11118e422021-12-02T01:33:10ZA pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery1176-91141178-2013https://doaj.org/article/34c95ebaafa74950afdaf49b11118e422012-02-01T00:00:00Zhttp://www.dovepress.com/a-ph-sensitive-multifunctional-gene-carrier-assembled-via-layer-by-lay-a9309https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Peng Li, Donghua Liu, Lei Miao, Chunxi Liu, Xiaoli Sun, Yongjun Liu, Na ZhangSchool of Pharmaceutical Science, Shandong University, Jinan, Shandong, People&rsquo;s Republic of ChinaBackground: The success of gene therapy asks for the development of multifunctional vectors that could overcome various gene delivery barriers, such as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer technique is an efficient method with easy operation which can be used for the assembly of multifunctional gene carriers. This work describes a pH-sensitive multifunctional gene vector that offered long circulation property but avoided the inhibition of tumor cellular uptake of gene carriers associated with the use of polyethylene glycol.Methods: Deoxyribonucleic acid (DNA) was firstly condensed with protamine into a cationic core which was used as assembly template. Then, additional layers of anionic DNA, cationic liposomes, and o-carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via layer-by-layer technique and finally the multifunctional vector called CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For in vitro test, the cytotoxicity and transfection investigation was carried out on HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected into tumor-bearing mice and the tumor cells were isolated for fluorescence determination of transfection efficiency.Results: CMCS-CLDPD had ellipsoidal shapes and showed &ldquo;core-shell&rdquo; structure which showed stabilization property in serum and effective protection of DNA from nuclease degradation. In vitro and in vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the outermost layer of CMCS fell off in the tumor tissue, which could not only protect CMCS-CLDPD from serum interaction but also enhance gene transfection efficiency.Conclusion: These results demonstrated that multifunctional CMCS-CLDPD had pH-sensitivity, which may provide a new approach for the antitumor gene delivery.Keywords: layer-by-layer, multifunctional nanovector, pH-sensitivity, gene deliveryLi PLiu DHMiao LLiu CXSun XLLiu YJZhang NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 925-939 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li P Liu DH Miao L Liu CX Sun XL Liu YJ Zhang N A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
description	Peng Li, Donghua Liu, Lei Miao, Chunxi Liu, Xiaoli Sun, Yongjun Liu, Na ZhangSchool of Pharmaceutical Science, Shandong University, Jinan, Shandong, People&rsquo;s Republic of ChinaBackground: The success of gene therapy asks for the development of multifunctional vectors that could overcome various gene delivery barriers, such as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer technique is an efficient method with easy operation which can be used for the assembly of multifunctional gene carriers. This work describes a pH-sensitive multifunctional gene vector that offered long circulation property but avoided the inhibition of tumor cellular uptake of gene carriers associated with the use of polyethylene glycol.Methods: Deoxyribonucleic acid (DNA) was firstly condensed with protamine into a cationic core which was used as assembly template. Then, additional layers of anionic DNA, cationic liposomes, and o-carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via layer-by-layer technique and finally the multifunctional vector called CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For in vitro test, the cytotoxicity and transfection investigation was carried out on HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected into tumor-bearing mice and the tumor cells were isolated for fluorescence determination of transfection efficiency.Results: CMCS-CLDPD had ellipsoidal shapes and showed &ldquo;core-shell&rdquo; structure which showed stabilization property in serum and effective protection of DNA from nuclease degradation. In vitro and in vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the outermost layer of CMCS fell off in the tumor tissue, which could not only protect CMCS-CLDPD from serum interaction but also enhance gene transfection efficiency.Conclusion: These results demonstrated that multifunctional CMCS-CLDPD had pH-sensitivity, which may provide a new approach for the antitumor gene delivery.Keywords: layer-by-layer, multifunctional nanovector, pH-sensitivity, gene delivery
format	article
author	Li P Liu DH Miao L Liu CX Sun XL Liu YJ Zhang N
author_facet	Li P Liu DH Miao L Liu CX Sun XL Liu YJ Zhang N
author_sort	Li P
title	A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
title_short	A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
title_full	A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
title_fullStr	A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
title_full_unstemmed	A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
title_sort	ph-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/34c95ebaafa74950afdaf49b11118e42
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A pH-sensitive multifunctional gene carrier assembled via layer-by-layer technique for efficient gene delivery

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