Efficacy of inverso isomer of CendR peptide on tumor tissue penetration

• 来源期刊: 药学学报（英文版）
• 关键词: Inverso isomer CendR peptide Neuropilin-1 (NRP-1) Tumor penetration Gemcitabine
• 年，卷（期）: 2018,（5）
• 页码范围: 825-832
• 页数: 8页
• 语种: 英文

摘要

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects.C-end nile (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues via binding to neuropilin-1 (NRP-1),thus aiding in drug delivery.In this study,we selected one of the CendR peptides (sequence RGERPPR) as the parent L-peptide and substituted D-amino acids for the L-amino acids to synthesize its inverso peptide D(RGERPPR).We investigated the NRP-1 binding activity and tumorpeaetrating ability of D(RGERPPR).We found that the binding affinity of D(RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR.Evans Blue tests revealed that D(RGERPPR) exhibited improved tumor-penetrating ability in C6,U87 and A549 tumor-bearing nude mice.Using nude mice bearing A549 xenograft tumors as a model,we found that the rate of tumor growth in the group co-administered with D(RGERPPR) and gemcitabine (Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate (TSR％) of 55.4％.Together,our results demonstrate that D(RGERPPR) is a potential tumor-penetrating peptide.