Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer

Jianfeng Liu1,2, Jinjian Liu2, Liping Chu2, Yanming Wang3, Yajun Duan1, Lina Feng2, Cuihong Yang1, Ling Wang3, Deling Kong11The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjian, People's Republic of China; 2Tianjin Key Lab...

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Autores principales: Liping Chu, Jinjian Liu, Jianfeng Liu, et al
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Publicado: Dove Medical Press 2010
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spelling oai:doaj.org-article:d49dab07b98b4a788b5f38526dd0dc472021-12-02T05:02:10ZNovel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer1176-91141178-2013https://doaj.org/article/d49dab07b98b4a788b5f38526dd0dc472010-12-01T00:00:00Zhttp://www.dovepress.com/novel-peptidendashdendrimer-conjugates-as-drug-carriers-for-targeting--a5952https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jianfeng Liu1,2, Jinjian Liu2, Liping Chu2, Yanming Wang3, Yajun Duan1, Lina Feng2, Cuihong Yang1, Ling Wang3, Deling Kong11The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjian, People's Republic of China; 2Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjian, People's Republic of China; 3College of Pharmacy, Nankai University, Tianjin, People's Republic of ChinaAbstract: Phage display technology has been demonstrated to be a powerful tool for screening useful ligands that are capable of specifically binding to biomarkers on the surface of tumor cells. The ligands found by this technique, such as peptides, have been successfully applied in the fields of early cancer diagnostics and chemotherapy. In this study, a novel nonsmall cell lung cancer-targeting peptide (LCTP, sequence RCPLSHSLICY) was screened in vivo using a Ph.D.-C7CTM phage display library. In order to develop a universal tumor-targeting drug carrier, the LCTP and fluorescence-labeled molecule (FITC) were conjugated to an acetylated polyamidoamine (PAMAM) dendrimer of generation 4 (G4) to form a PAMAM–Ac–FITC–LCTP conjugate. The performance of the conjugate was first tested in vitro. In vitro results of cell experiments analyzed by flow cytometry and inverted fluorescence microscopy indicated that PAMAM–Ac–FITC–LCTP was enriched more in NCI-H460 cells than in 293T cells, and cellular uptake was both time- and dose-dependent. The tissue distribution of the conjugate in athymic mice with lung cancer xenografts was also investigated to test the targeting efficiency of PAMAM–Ac–FITC–LCTP in vivo. The results showed that LCTP can effectively facilitate the targeting of PAMAM–Ac–FITC–LCTP to nonsmall cell lung cancer cells and tumors. These results suggest that the LCTP-conjugated PAMAM dendrimer might be a promising drug carrier for targeted cancer diagnosis and treatment.Keywords: polyamidoamine dendrimer, in vivo phage display, targeted drug delivery, peptide, nonsmall cell lung cancer  Liping ChuJinjian LiuJianfeng Liuet alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 59-69 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Liping Chu
Jinjian Liu
Jianfeng Liu
et al
Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
description Jianfeng Liu1,2, Jinjian Liu2, Liping Chu2, Yanming Wang3, Yajun Duan1, Lina Feng2, Cuihong Yang1, Ling Wang3, Deling Kong11The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjian, People's Republic of China; 2Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjian, People's Republic of China; 3College of Pharmacy, Nankai University, Tianjin, People's Republic of ChinaAbstract: Phage display technology has been demonstrated to be a powerful tool for screening useful ligands that are capable of specifically binding to biomarkers on the surface of tumor cells. The ligands found by this technique, such as peptides, have been successfully applied in the fields of early cancer diagnostics and chemotherapy. In this study, a novel nonsmall cell lung cancer-targeting peptide (LCTP, sequence RCPLSHSLICY) was screened in vivo using a Ph.D.-C7CTM phage display library. In order to develop a universal tumor-targeting drug carrier, the LCTP and fluorescence-labeled molecule (FITC) were conjugated to an acetylated polyamidoamine (PAMAM) dendrimer of generation 4 (G4) to form a PAMAM–Ac–FITC–LCTP conjugate. The performance of the conjugate was first tested in vitro. In vitro results of cell experiments analyzed by flow cytometry and inverted fluorescence microscopy indicated that PAMAM–Ac–FITC–LCTP was enriched more in NCI-H460 cells than in 293T cells, and cellular uptake was both time- and dose-dependent. The tissue distribution of the conjugate in athymic mice with lung cancer xenografts was also investigated to test the targeting efficiency of PAMAM–Ac–FITC–LCTP in vivo. The results showed that LCTP can effectively facilitate the targeting of PAMAM–Ac–FITC–LCTP to nonsmall cell lung cancer cells and tumors. These results suggest that the LCTP-conjugated PAMAM dendrimer might be a promising drug carrier for targeted cancer diagnosis and treatment.Keywords: polyamidoamine dendrimer, in vivo phage display, targeted drug delivery, peptide, nonsmall cell lung cancer 
format article
author Liping Chu
Jinjian Liu
Jianfeng Liu
et al
author_facet Liping Chu
Jinjian Liu
Jianfeng Liu
et al
author_sort Liping Chu
title Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
title_short Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
title_full Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
title_fullStr Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
title_full_unstemmed Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
title_sort novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer
publisher Dove Medical Press
publishDate 2010
url https://doaj.org/article/d49dab07b98b4a788b5f38526dd0dc47
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AT jianfengliu novelpeptideampndashdendrimerconjugatesasdrugcarriersfortargetingnonsmallcelllungcancer
AT etal novelpeptideampndashdendrimerconjugatesasdrugcarriersfortargetingnonsmallcelllungcancer
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