Efficacy of inverso isomer of CendR peptide on tumor tissue penetration
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 via bindi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-09-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383517306056 |
| _version_ | 1818060329239707648 |
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| author | Ruifeng Wang Qing Shen Xue Li Cao Xie Weiyue Lu Songli Wang Jing Wang Dongli Wang Min Liu |
| author_facet | Ruifeng Wang Qing Shen Xue Li Cao Xie Weiyue Lu Songli Wang Jing Wang Dongli Wang Min Liu |
| author_sort | Ruifeng Wang |
| collection | DOAJ |
| description | 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 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 tumor-penetrating 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. KEY WORDS: Inverso isomer, CendR peptide, Neuropilin-1 (NRP-1), Tumor penetration, Gemcitabine |
| first_indexed | 2024-12-10T13:30:41Z |
| format | Article |
| id | doaj.art-af13f1dfabc044e08a421b57287cafe0 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-10T13:30:41Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-af13f1dfabc044e08a421b57287cafe02022-12-22T01:46:59ZengElsevierActa Pharmaceutica Sinica B2211-38352018-09-0185825832Efficacy of inverso isomer of CendR peptide on tumor tissue penetrationRuifeng Wang0Qing Shen1Xue Li2Cao Xie3Weiyue Lu4Songli Wang5Jing Wang6Dongli Wang7Min Liu8Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaKey Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaCorresponding author.; Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, ChinaThe 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 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 tumor-penetrating 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. KEY WORDS: Inverso isomer, CendR peptide, Neuropilin-1 (NRP-1), Tumor penetration, Gemcitabinehttp://www.sciencedirect.com/science/article/pii/S2211383517306056 |
| spellingShingle | Ruifeng Wang Qing Shen Xue Li Cao Xie Weiyue Lu Songli Wang Jing Wang Dongli Wang Min Liu Efficacy of inverso isomer of CendR peptide on tumor tissue penetration Acta Pharmaceutica Sinica B |
| title | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration |
| title_full | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration |
| title_fullStr | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration |
| title_full_unstemmed | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration |
| title_short | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration |
| title_sort | efficacy of inverso isomer of cendr peptide on tumor tissue penetration |
| url | http://www.sciencedirect.com/science/article/pii/S2211383517306056 |
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