Efficacy of inverso isomer of CendR peptide on tumor tissue penetration.
10.1016/j.apsb.2018.06.006
- Author:
Ruifeng WANG
1
;
Qing SHEN
1
;
Xue LI
1
;
Cao XIE
1
;
Weiyue LU
1
;
Songli WANG
1
;
Jing WANG
1
;
Dongli WANG
1
;
Min LIU
1
Author Information
1. Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
CendR peptide;
Gemcitabine;
Inverso isomer;
Neuropilin-1 (NRP-1);
Tumor penetration
- From:
Acta Pharmaceutica Sinica B
2018;8(5):825-832
- CountryChina
- Language:English
-
Abstract:
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 rule (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues 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 (RGERPPR). We investigated the NRP-1 binding activity and tumor-penetrating ability of (RGERPPR). We found that the binding affinity of (RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that (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 (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 (RGERPPR) is a potential tumor-penetrating peptide.
