Abstract
Development of drug delivery systems for cancer therapy is a crucial issue. Previously, some peptides were designed as tumor homing cell-penetrating peptides with antitumor activities. In this study, dual function dendrimers with tumor targeting activities and antitumor effects were designed using the tumor targeting CPP44 peptide for acute myelogenous leukemia (AML) and the antitumor p16INK4a peptide. Two types of peptide–dendrimer conjugates were synthesized. One was a CPP44-linked p16INK4a peptide-conjugated dendrimer (tandem linked dendrimer) and the other was a dendrimer conjugated with separate CPP44 and p16INK4a peptides (parallel linked dendrimer). In addition, a peptide cathepsin B substrate was linked to the antitumor p16INK4a peptide to release it from the carriers. These peptide–dendrimer conjugates produced more effective antitumor effects than a CPP44-linked p16INK4a peptide. The parallel linked dendrimer showed less association with AML cells than the tandem linked dendrimer, but had greater antitumor effects. This suggested that both cellular uptake and antitumor peptide cleavage affected the antitumor activities of dual functional peptide-conjugated dendrimers.
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This manuscript was supported by a grant-in-aid from the Japan Society for the Promotion of Science (JSPS) for Scientific Research (C) (No. 26410227) and Scientific Research (B) (No. 25290062).
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Kojima, C., Saito, K. & Kondo, E. Design of peptide–dendrimer conjugates with tumor homing and antitumor effects. Res Chem Intermed 44, 4685–4695 (2018). https://doi.org/10.1007/s11164-018-3280-9
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DOI: https://doi.org/10.1007/s11164-018-3280-9