Induced Cell Morphology Electroporation via EphA2 Ligand
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Solution Overview
Problem
Traditional electroporation methods cause excessive damage to surrounding normal tissue, making them unsuitable for treating aberrant cells outside tumor margins or interspersed with healthy tissue, particularly in sensitive areas like the brain, due to non-selective cell manipulation and treatment.
Innovation Solution
The use of high-frequency irreversible electroporation (H-FIRE) pulse trains, combined with EphA2 receptor ligand administration, to selectively target and ablate cancer cells by altering their morphology, thereby increasing the nucleus-to-cytoplasm ratio, making them more susceptible to treatment while sparing normal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional electroporation modalities are used to treat aberrant cells, then treatment effectiveness for masses of aberrant cells is achieved, but damage to surrounding normal tissue becomes excessive
Solution Approach 1:
The patent applies local quality by inducing specific morphological changes in cancer cells through EphA2 receptor ligand treatment, making these cells locally distinct from normal cells. This enables selective targeting of cancer cells with altered morphology (increased nucleus-to-cytoplasm ratio) while sparing normal tissue, directly resolving the contradiction between treatment effectiveness and protection of surrounding normal tissue
Solution Approach 2:
The patent changes the physical parameter of cell morphology by treating cancer cells with EphA2 receptor ligands, which alters their nucleus-to-cytoplasm ratio. This parameter change makes cancer cells more susceptible to H-FIRE electroporation while normal cells remain unaffected, solving the contradiction between effective cancer treatment and avoidance of normal tissue damage
2Adaptability or versatility
If traditional electroporation is applied to treat aberrant cells outside tumor margin or interspersed with normal tissue, then treatment coverage is improved, but damage to sensitive tissue becomes excessive
Solution Approach 1:
The patent enables treatment of aberrant cells scattered throughout sensitive tissue by creating local morphological differences through EphA2 ligand treatment. This allows H-FIRE electroporation to selectively target individual cancer cells anywhere in the tissue without causing excessive damage to surrounding sensitive areas, improving both treatment coverage and safety
Solution Approach 2:
The EphA2 receptor ligand acts as an intermediary that mediates between the electroporation treatment and the cancer cells. It selectively marks cancer cells for treatment by inducing morphological changes, allowing the H-FIRE energy to be delivered selectively to cancer cells while protecting normal sensitive tissue from damage
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
This approach enhances the selectivity of electroporation, allowing for effective treatment of cancer cells with reduced damage to healthy tissue, as demonstrated by increased sensitivity of cancer cells to H-FIRE and maintained viability of normal cells.
Implementation Method 1
contacting a cell responsive to an EphA2 receptor ligand with an amount of an EphA2 receptor ligand
Implementation Method 2
applying to the cell responsive to the EphA2 receptor ligand, a high-frequency irreversible electroporation (H-FIRE) pulse train
Implementation Method 3
Each electric waveform pulse can have a carrier frequency in the range of about 1 KHz to about 1 MHz
Data Source
AI summary
Described herein are methods of electroporation that can include the steps of contacting a cell that is responsive to an EphA2 receptor ligand with an amount of an EphA2 receptor ligand and applying high-frequency irreversible electroporation to the cell. Also described herein are methods of treating cancer in a subject in need thereof, wherein the methods can include the steps of administering an amount of an EphA2 receptor ligand and applying high-frequency irreversible electroporation to a location on or within the subject.