Abstract:
:In this study, a peptide-drug conjugate was designed and synthesized by connecting a transferrin receptor (TfR)-targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N-succinimidyl-3-maleimidopropionate (SMP) as the cross-linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L-O2 normal liver cells expressing low level of TfR; most of the BP9a-DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L-O2 cells was much less than that of free DOX. Meanwhile, the BP9a-DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L-O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR-targeted peptide vector for selective drug delivery.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Li S,Zhao H,Fan Y,Zhao G,Wang R,Wen F,Wang J,Wang X,Wang Y,Gao Ydoi
10.1111/cbdd.13613subject
Has Abstractpub_date
2020-01-01 00:00:00pages
58-65issue
1eissn
1747-0277issn
1747-0285journal_volume
95pub_type
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