10.1021/mp100185f.s001 Liang Han Liang Han Rongqin Huang Rongqin Huang Shuhuan Liu Shuhuan Liu Shixian Huang Shixian Huang Chen Jiang Chen Jiang Peptide-Conjugated PAMAM for Targeted Doxorubicin Delivery to Transferrin Receptor Overexpressed Tumors American Chemical Society 2010 T 7 Transferrin Receptor Overexpressed TumorsThe purpose Targeted Doxorubicin Delivery DOX PEG NP vivo antitumor studies Tf HAIYPRH PAMAM IC 2010-12-06 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Peptide_Conjugated_PAMAM_for_Targeted_Doxorubicin_Delivery_to_Transferrin_Receptor_Overexpressed_Tumors/2707402 The purpose of this work was to evaluate the potential of HAIYPRH (T7) peptide as a ligand for constructing tumor-targeting drug delivery systems. T7 could target to transferrin-receptor (TfR) through a cavity on the surface of TfR and then transport into cells via endocytosis with the help of transferrin (Tf). In this study, T7-conjugated poly(ethylene glycol) (PEG)-modified polyamidoamine dendrimer (PAMAM) (PAMAM-PEG-T7) was successfully synthesized and further loaded with doxorubicin (DOX), formulating PAMAM-PEG-T7/DOX nanoparticles (NPs). In vitro, almost 100% of DOX was released during 2 h in pH 5.5, while only 55% of DOX was released over 48 h in pH 7.4. The cellular uptake of DOX could be significantly enhanced when treated with T7-modified NPs in the presence of Tf. Also, the in vitro antitumor effect was enhanced markedly. The IC<sub>50</sub> of PAMAM-PEG-T7/DOX NPs with Tf was 231.5 nM, while that of NPs without Tf was 676.7 nM. T7-modified NPs could significantly enhance DOX accumulation in the tumor by approximately 1.7-fold compared to that of unmodified ones and by approximately 5.3-fold compared to that of free DOX. For in vivo antitumor studies, tumor growth of mice treated with PAMAM-PEG-T7/DOX NPs was significantly inhibited compared to that of mice treated with PAMAM-PEG/DOX NPs and saline. The study provides evidence that PAMAM-PEG-T7 can be applied as a potential tumor-targeting drug delivery system. T7 may be a promising ligand for targeted drug delivery to the tumor.