Peptide-Conjugated PAMAM for Targeted Doxorubicin Delivery to Transferrin Receptor Overexpressed Tumors

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• 作者：Liang Han ; Rongqin Huang ; Shuhuan Liu ; Shixian Huang ; Chen Jiang
• 刊名：Molecular Pharmaceutics
• 出版年：2010
• 出版时间：December 6, 2010
• 年：2010
• 卷：7
• 期：6
• 页码：2156-2165
• 全文大小：307K
• 年卷期：v.7,no.6(December 6, 2010)
• ISSN：1543-8392

文摘

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 IC₅₀ 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.

Keywords:

Doxorubicin; PAMAM; HAIYPRH; tumor-targeting; enhanced permeability and retention; receptor-mediated endocytosis