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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Cell penetrating elastin-like polypeptides for therapeutic peptide delivery
Gene L Bidwell1, Drazen Raucher
1University of Mississippi Medical Center, Department of Biochemistry, Jackson, 39216, USA. gbidwell@umc.edu
Abstract:
Current treatment of solid tumors is limited by side effects that result from the non-specific delivery of drugs to the tumor site. Alternative targeted therapeutic approaches for localized tumors would significantly reduce systemic toxicity. Peptide therapeutics are a promising new strategy for targeted cancer therapy because of the ease of peptide design and the specificity of peptides for their intracellular molecular targets. However, the utility of peptides is limited by their poor pharmacokinetic parameters and poor tissue and cellular membrane permeability in vivo. This review article summarizes the development of elastin-like polypeptide (ELP) as a potential carrier for thermally targeted delivery of therapeutic peptides (TP), and the use of cell penetrating peptides (CPP) to enhance the intracellular delivery of the ELP-fused TPs. CPP-fused ELPs have been used to deliver a peptide inhibitor of c-Myc function and a peptide mimetic of p21 in several cancer models in vitro, and both polypeptides are currently yielding promising results in in vivo models of breast and brain cancer.
Insights
This study explores elastin-like polypeptides (ELPs) as carriers for targeted cancer therapy. By fusing therapeutic peptides (TPs) with cell-penetrating peptides (CPPs), researchers aim to improve drug delivery and reduce side effects for solid tumors.
Area of Science:
- Biotechnology
- Oncology
- Drug Delivery
Background:
- Current solid tumor treatments face limitations due to non-specific drug delivery and significant systemic toxicity.
- Peptide therapeutics offer targeted cancer treatment potential but suffer from poor pharmacokinetics and cellular permeability.
- Developing targeted delivery systems is crucial to overcome these limitations and enhance therapeutic efficacy.
Purpose of the Study:
- To review the development of elastin-like polypeptides (ELPs) as carriers for thermally targeted delivery of therapeutic peptides (TPs).
- To explore the use of cell-penetrating peptides (CPPs) to enhance intracellular delivery of ELP-fused TPs.
- To assess the potential of CPP-fused ELPs in preclinical cancer models.
Main Methods:
- Development and characterization of elastin-like polypeptide (ELP) constructs.
- Fusion of therapeutic peptides (TPs) with ELPs and cell-penetrating peptides (CPPs).
- In vitro and in vivo evaluation of ELP-based drug delivery systems in various cancer models.
Main Results:
- CPP-fused ELPs successfully delivered peptide inhibitors of c-Myc and p21 in vitro.
- These novel constructs demonstrated promising results in preclinical models of breast and brain cancer.
- The thermally targeted delivery approach using ELPs shows potential for localized cancer treatment.
Conclusions:
- Elastin-like polypeptides (ELPs) fused with cell-penetrating peptides (CPPs) represent a promising strategy for targeted cancer therapy.
- This approach enhances intracellular delivery of therapeutic peptides, potentially reducing systemic toxicity.
- Further development of ELP-CPP conjugates holds significant potential for treating localized solid tumors.
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