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Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to
Nemany A N Hanafy1, Isabel Fabregat2, Stefano Leporatti3
1Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt.
Abstract:
: 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.
Insights
Encapsulating peptides P17 and P144 in polymer hybrid protein moieties may improve their therapeutic potential. This nano-delivery strategy aims to enhance targeted therapy and overcome limitations of hydrophobic molecules like P144.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Transforming growth factor-beta (TGFβ1) is a key regulator of cellular processes and an oncogenic factor in advanced cancers, promoting invasion and metastasis.
- Existing TGFβ1 inhibitors, peptides P17 and P144, face limitations including poor target selection, immunogenicity, cytotoxicity, and poor solubility (P144).
Purpose of the Study:
- To develop nano-delivery strategies for peptides P17 and P144 to enhance targeted therapy.
- To overcome the poor dissolution of P144 and protect normal cells from potential cytotoxicity.
- To improve cellular penetration and therapeutic efficacy of these TGFβ1 inhibitors.
Main Methods:
- Peptides P17 and P144 were encapsulated in polymer hybrid protein moieties.
- Assembly of the peptide-polymer constructs was analyzed using Transmission Electron Microscopy (TEM), microplate spectrum analysis, and fluorescence microscopy.
- Biological efficiency was assessed by analyzing SMAD phosphorylation via Western blot.
Main Results:
- The encapsulation of peptides P17 and P144 within polymer hybrid protein moieties was successfully achieved.
- Characterization techniques confirmed the assembly and structure of the nano-delivery system.
- Preliminary results suggest that encapsulation may improve the therapeutic potential of the peptides.
Conclusions:
- Nano-encapsulation presents a promising strategy to enhance the therapeutic applications of TGFβ1-inhibiting peptides P17 and P144.
- This approach addresses key limitations such as poor solubility and potential cytotoxicity, paving the way for improved cancer therapies targeting the TGFβ1 pathway.
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