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
âą
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
PAMAMâAcâFITCâLCTP 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 PAMAMâAcâFITCâLCTP 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 PAMAMâAcâFITCâLCTP in vivo.
The results showed that LCTP can effectively facilitate the targeting of
PAMAMâAcâFITCâLCTP 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.