Selective Delivery Molecule with Cleavable Linker for Targeted Imaging

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Solution Overview

Problem

Current selective delivery molecules face challenges with rapid pharmacokinetic clearance, broad distribution, and non-specific uptake in non-target tissues, leading to reduced accumulation in target tissues and poor bio-distribution for imaging agents, resulting in low contrast in target tissues compared to background tissues.

Innovation Solution

The development of selective delivery molecules with a cleavable linker, a peptide sequence comprising acidic and basic amino acids, and a polyethylene glycol (PEG) polymer, which allows targeted delivery of imaging agents by binding to specific tissues, such as cancerous tissues, using fluorescence resonance energy transfer (FRET) pairs like Cy5 and Cy7, enabling enhanced visualization and retention in target tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If selective delivery molecules are used for targeted delivery, then accumulation in target tissues is improved, but rapid pharmacokinetic clearance and broad distribution reduce effectiveness

Engineering Contradiction:

Improveaccumulation in target tissuesVSAvoidpharmacokinetic clearance and broad distribution

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The selective delivery molecule is segmented into distinct functional domains: a targeting moiety (peptide sequence with acidic and basic amino acids) for specific tissue binding, a cleavable linker for controlled release, and a PEG polymer for circulation stability. This segmentation allows each component to optimize its function independently, resolving the contradiction between targeted accumulation and pharmacokinetic clearance.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention uses a composite molecular structure combining peptide sequences (with specific acidic and basic amino acid ratios), cleavable linkers, and PEG polymers. This composite design creates a molecule that simultaneously achieves stable circulation, targeted accumulation, and controlled release, overcoming the limitations of single-component delivery systems.

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If imaging agents are delivered to target tissues, then visualization capability is improved, but non-specific uptake in non-target tissues reduces contrast

Engineering Contradiction:

Improvevisualization capability and contrastVSAvoidnon-specific uptake in non-target tissues

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The peptide sequence is designed with specific local compositions of acidic and basic amino acids (5-9 acidic, 7-9 basic) to create localized positive charge regions that specifically interact with negatively charged cell surfaces in target tissues. This local quality optimization ensures specific binding at the target site while minimizing non-specific uptake elsewhere, thereby improving contrast.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If peptide sequences with acidic and basic amino acids are used for targeting, then tissue binding specificity is improved, but molecular structure complexity increases

Engineering Contradiction:

Improvetissue binding specificityVSAvoidmolecular structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention optimizes specific parameters of the peptide sequence, including the number of acidic amino acids (5-9), basic amino acids (7-9), and their specific arrangements, to achieve optimal tissue binding specificity. By systematically adjusting these parameters rather than using complex structural designs, the molecule achieves high specificity with relatively simple sequence-based complexity.

Inventive Principle:

Principle #35Parameter changes

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 accumulation of imaging agents in target tissues, improving contrast and allowing for effective visualization and diagnosis of cancerous tissues, while minimizing non-specific uptake, thereby improving the diagnostic accuracy and specificity of cancer detection.

Implementation Method 1

X is a cleavable linker... X is cleavable by a protease... X is cleavable by a matrix metalloproteinase

Methodology Applied

Scientific EffectProtease cleavage: Enzyme

Implementation Method 2

DA and DB are a pair of acceptor and donor fluorescent moieties that are capable of undergoing Försters/fluorescence resonance energy transfer with the other... DA and DB are Cy5 and Cy7

Methodology Applied

Scientific EffectFluorescence resonance energy transfer (FRET): Fluorescence

Data Source

PatentUS10570178B2Selective delivery molecules and methods of use

Publication Date: 2020.02.25 AVELAS ACQUISITION CORP

AI summary

Disclosed herein is a selective delivery molecule comprising: (a) an acidic sequence (portion A) which is effective to inhibit or prevent the uptake into cells or tissue retention, (b) a molecular transport or retention sequence (portion B), and (c) a linker between portion A and portion B, and (d) at least one cargo moiety.