EphB4-Binding Therapeutic Peptides for Tumor Growth and Angiogenesis
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Solution Overview
Problem
Current therapies lack small-molecule-based, dual-function EphB4-binding peptides for treating cancers, particularly those that target EphB4 signaling to inhibit tumor cell proliferation and endothelial cell angiogenesis.
Innovation Solution
Development of non-natural peptides, such as BIDEN-AP, which act as bi-directional ephrin agonists, selectively binding to EphB4 and promoting forward signaling to suppress tumor growth and angiogenesis, and can be conjugated with nanocarriers or cytotoxic drugs for targeted delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If monoclonal antibodies, soluble fusion proteins, or small-molecule kinase inhibitors are used to inhibit reverse EphB4-to-EFNB2 signaling, then angiogenesis is suppressed, but no small-molecule-based dual-function EphB4-binding peptides are available and therapeutic options remain limited
Solution Approach 1:
The invention changes the molecular parameters by developing small-molecule peptides (e.g., BIDEN-AP) with specific amino acid sequences that can bind to EphB4, transitioning from large biomolecules (monoclonal antibodies, fusion proteins) to compact small-molecule peptides while maintaining or enhancing therapeutic functionality
Solution Approach 2:
The small-molecule peptides are designed to perform multiple functions: binding to EphB4, suppressing forward signaling to inhibit tumor cell proliferation, and blocking reverse signaling to suppress angiogenesis, thereby providing dual-function therapy in a single molecule
2Reliability
If therapeutic peptides are designed to bind EphB4 and suppress tumor growth, then anti-tumor activity is achieved, but the peptides must be conjugated with nanocarriers or cytotoxic drugs for enhanced delivery and potency
Solution Approach 1:
The invention uses nanocarriers (e.g., core-crosslinked polymeric micelles) as intermediaries to deliver therapeutic peptides to target sites, facilitating enhanced penetration, stability, and controlled release while reducing systemic toxicity
Solution Approach 2:
The invention creates composite therapeutic systems by conjugating small-molecule peptides with nanocarriers and/or cytotoxic drugs, combining the specificity of peptide binding with the delivery advantages of nanoparticles and the potency of cytotoxic agents
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
BIDEN-AP and its nano-conjugate CCPM-BIDEN-AP significantly reduce tumor growth and inhibit angiogenesis by downregulating EMT and angiogenic pathways, demonstrating potent anti-tumor activity both in vitro and in vivo.
Implementation Method 1
BIDEN-AP was selectively internalized via receptor-mediated endocytosis and suppressed invasion and EMT of ovarian cancer cells
Implementation Method 2
BIDEN-AP was selectively internalized via receptor-mediated endocytosis
Implementation Method 3
Both BIDEN-AP and CCPM-BIDEN-AP compromised angiogenesis by downregulating EMT and angiogenic pathways
Data Source
AI summary
Provided herein are therapeutic peptides. In some aspects, therapeutic peptides are provided that can alter EphB4/EFNB2 signaling and can be used to treat a cancer. In some embodiments, the peptides are comprised in nanoparticles, such as core-cross-linked polymeric micelles (CCPM).