title: Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors.
abstract: 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(50) 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Rongqin
authors.initials: R
authors.lastname: Huang
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Liu
authors.forename: Shixian
authors.initials: S
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D008024:Ligands; D010455:Peptides; C531249:Poly(amidoamine); D011073:Polyamines; D011092:Polyethylene Glycols; D004317:Doxorubicin