Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization
Transforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasiv...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/5/421 |
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| author | Nemany A. N. Hanafy Isabel Fabregat Stefano Leporatti Maged El Kemary |
| author_facet | Nemany A. N. Hanafy Isabel Fabregat Stefano Leporatti Maged El Kemary |
| author_sort | Nemany A. N. Hanafy |
| collection | DOAJ |
| description | Transforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone to move into the metastatic process. This finding has received great attention for discovering new therapeutic molecules against the TGFβ1 pathway. Among many TGFβ1 inhibitors, peptides (P17 and P144) were designed to block the TGFβ1 pathway. However, their therapeutic applications have limited use, due to lack of selection for their targets and their possible recognition by the immune system and further due to their potential cytotoxicity on healthy cells. Besides that, P144 is a highly hydrophobic molecule with less dissolution even in organic solution. Here, we aimed to overcome the dissolution of P144, as well as design nano-delivery strategies to protect normal cells, to increase cellular penetration and to raise the targeted therapy of both P17 and P144. Peptides were encapsulated in moieties of polymer hybrid protein. Their assembly was investigated by TEM, microplate spectrum analysis and fluorescence microscopy. SMAD phosphorylation was analyzed by Western blot as a hallmark of their biological efficiency. The results showed that the encapsulation of P17 and P144 might improve their potential therapeutic applications. |
| first_indexed | 2024-03-10T20:03:08Z |
| format | Article |
| id | doaj.art-160765efe5404e4e9ca2c57a717c074b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:03:08Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-160765efe5404e4e9ca2c57a717c074b2023-11-19T23:23:01ZengMDPI AGPharmaceutics1999-49232020-05-0112542110.3390/pharmaceutics12050421Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their FunctionalizationNemany A. N. Hanafy0Isabel Fabregat1Stefano Leporatti2Maged El Kemary3Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh 33516, EgyptBellvitge Biomedical Research Institute (IDIBELL), University of Barcelona (UB) and CIBEREHD, Gran Via de l’Hospitalet, 199, Hospitalet de Llobregat, 08908 Barcelona, SpainCNR NANOTEC-Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, ItalyNanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh 33516, EgyptTransforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone to move into the metastatic process. This finding has received great attention for discovering new therapeutic molecules against the TGFβ1 pathway. Among many TGFβ1 inhibitors, peptides (P17 and P144) were designed to block the TGFβ1 pathway. However, their therapeutic applications have limited use, due to lack of selection for their targets and their possible recognition by the immune system and further due to their potential cytotoxicity on healthy cells. Besides that, P144 is a highly hydrophobic molecule with less dissolution even in organic solution. Here, we aimed to overcome the dissolution of P144, as well as design nano-delivery strategies to protect normal cells, to increase cellular penetration and to raise the targeted therapy of both P17 and P144. Peptides were encapsulated in moieties of polymer hybrid protein. Their assembly was investigated by TEM, microplate spectrum analysis and fluorescence microscopy. SMAD phosphorylation was analyzed by Western blot as a hallmark of their biological efficiency. The results showed that the encapsulation of P17 and P144 might improve their potential therapeutic applications.https://www.mdpi.com/1999-4923/12/5/421transforming growth factorsproliferationpolymer hybrid protein |
| spellingShingle | Nemany A. N. Hanafy Isabel Fabregat Stefano Leporatti Maged El Kemary Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization Pharmaceutics transforming growth factors proliferation polymer hybrid protein |
| title | Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization |
| title_full | Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization |
| title_fullStr | Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization |
| title_full_unstemmed | Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization |
| title_short | Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization |
| title_sort | encapsulating tgf β1 inhibitory peptides p17 and p144 as a promising strategy to facilitate their dissolution and to improve their functionalization |
| topic | transforming growth factors proliferation polymer hybrid protein |
| url | https://www.mdpi.com/1999-4923/12/5/421 |
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