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

Authors Liu J, liu J, Chu L, Wang, Duan, Feng, Yang C, Wang, Kong D

Published 22 December 2010 Volume 2011:6 Pages 59—69

DOI https://doi.org/10.2147/IJN.S14601

Review by Single-blind

Peer reviewer comments 4


Jianfeng Liu1,2, Jinjian Liu2, Liping Chu2, Yanming Wang3, Yajun Duan1, Lina Feng2, Cuihong Yang1, Ling Wang3, Deling Kong1
1The 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 China

Abstract: 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
 

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