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

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.-C7C^™ 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

Supplementary Material

Figure S1 ¹H nuclear magnetic resonance spectrum (300 mHz,D₂O) of the acetylated polyamidoamine.

Figure S2 ¹H nuclear magnetic resonance spectrum (300 mHz,D₂O) of the fluorescence-labeled acetylated polyamidoamine.

Figure S3 ¹H nuclear magnetic resonance spectrum (300 mHz, D₂O) of the fluorescence-labeled acetylated polyamidoamine lung cancer targeting peptide.

Figure S4 Laser light-scattering assay results. The polyamidoamine particle size was about 7 nm (A) and the particle size of acetylated polyamidoamine (B) fluorescence-labeled acetylated polyamidoamine (C), and fluorescence-labeled acetylated polyamidoamine lung cancer targeting peptide (D) becomes bigger and bigger.

Acknowledgments

This study was financially support by the National Natural Science Foundation of China (30700178 and 20774050), the National Outstanding Youth Fund (30725030), Tianjin Natural Science Foundation (09JCYBJC13400), and the Development Foundation of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (SF0627, SF0823).

Disclosure

The authors report no conflicts of interest in this work.