pH-Sensitive Peptide Delivery for Acidic Tumor Tissue Targeting
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Solution Overview
Problem
Existing cancer treatments, such as PARP inhibitors, exhibit significant side effects when administered systemically due to their impact on both cancer and non-cancerous cells, and there is a need for targeted delivery to acidic or hypoxic diseased tissues to minimize these side effects.
Innovation Solution
Development of pH-sensitive peptides linked to therapeutic molecules via disulfide-containing linkers that selectively target and deliver compounds to acidic or hypoxic tissues, allowing for localized treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PARP inhibitors are administered systemically to treat cancer, then the therapeutic effect on cancer cells is improved, but side effects on non-cancerous cells increase
Solution Approach 1:
The patent applies local quality by modifying the PARP inhibitor with a pH-sensitive peptide that enables the drug to selectively accumulate in acidic tumor microenvironments. This creates a spatial difference in drug concentration and activity, allowing high therapeutic effect in cancer cells while minimizing exposure and side effects in normal cells with neutral pH
Solution Approach 2:
The pH-sensitive peptide acts as an intermediary that mediates between the PARP inhibitor and the target cancer cells. This peptide component recognizes and binds to acidic environments, facilitating selective delivery of the therapeutic agent to tumor tissues while protecting normal tissues from harmful effects
2Reliability
If DNA repair inhibitors are used to slow or terminate cancer cell replication, then the treatment efficacy is improved, but the replication of non-cancerous cells is also affected leading to side effects
Solution Approach 1:
By conjugating the DNA repair inhibitor with a pH-sensitive peptide, the patent creates a localized action mechanism where the inhibitor is activated or accumulated specifically in acidic tumor regions. This ensures that the harmful effect of DNA repair inhibition is confined to cancer cells while sparing normal cells with neutral pH environments
3Area of stationary object
If therapeutic compounds are administered systemically, then the coverage of diseased tissues is improved, but the exposure of normal cells to the compound increases
Solution Approach 1:
The pH-sensitive peptide modification transforms a systemic compound into one with localized action. While the compound can be administered systemically for broad coverage, the peptide component ensures that biological activity is restricted to acidic tumor microenvironments, creating a dissociation between distribution coverage and active exposure
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
Enhances the therapeutic efficacy of compounds by selectively targeting diseased tissues, reducing side effects on normal cells and improving treatment outcomes.
Implementation Method 1
R7 is a peptide capable of selectively delivering R8Q across a cell membrane having an acidic or hypoxic mantle in a pH dependent fashion
Implementation Method 2
Q is a linker comprising a disulfide
Data Source
AI summary
Compounds for treatment of diseases having acidic or hypoxic diseased tissues and pharmaceutical compositions comprising the compounds, as well as methods for making and using the compounds and compositions.