CXCR4-Targeting Peptide Conjugate for Internalization

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Solution Overview

Problem

Current conjugates for delivering therapeutic agents to CXCR4-expressing cells face inefficiencies in internalization, as they often rely on external binding and require increased CXCR4 expression, leading to potential tumor proliferation and limited internalization of therapeutic agents.

Innovation Solution

A conjugate comprising a targeting peptide with the sequence RRWCYRKCYKGYCYRKCR or functionally equivalent variants, capable of specifically binding to CXCR4 and promoting the internalization of therapeutic agents into CXCR4-expressing cells, facilitating endosomal escape and efficient delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional conjugates are used for delivering therapeutic agents to CXCR4-expressing cells, then targeting is achieved, but internalization efficiency is low and tumor proliferation may increase

Engineering Contradiction:

Improveinternalization efficiencyVSAvoidtumor proliferation risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of the targeting ligand by introducing a cleavable peptide linker between the CXCR4-targeting moiety and the therapeutic agent. This parameter change enables conditional release of the therapeutic agent after internalization, improving delivery efficiency while reducing off-target effects and tumor proliferation risks associated with conventional conjugates

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention extracts the targeting function from the therapeutic conjugate by using a separate CXCR4-binding peptide that can be internalized independently. This allows the therapeutic agent to be delivered efficiently to CXCR4-expressing cells without the harmful side effects of increased CXCR4 expression, as the targeting moiety is removed after fulfilling its delivery function

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If CXCR4 expression is increased on target cells to enhance conjugate binding, then targeting efficiency improves, but tumor proliferation is stimulated

Engineering Contradiction:

Improvetargeting efficiencyVSAvoidtumor proliferation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs a preliminary action by using a CXCR4-binding peptide that temporarily increases CXCR4 expression or activity only long enough to facilitate internalization of the conjugate. The harmful effect of increased CXCR4 expression is minimized because the peptide is designed to be internalized and degraded, preventing sustained stimulation of tumor cell proliferation

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention introduces a cleavable peptide linker as an intermediary between the CXCR4-targeting moiety and the therapeutic agent. This intermediary allows the conjugate to bind and internalize efficiently while protecting the therapeutic agent from premature release. After internalization, the linker is cleaved, separating the targeting function from the therapeutic function and eliminating the stimulus for further tumor proliferation

Inventive Principle:

Principle #24Intermediary (Mediator)

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

The conjugate achieves effective internalization and endosomal escape of therapeutic agents within CXCR4-expressing cells, enhancing the delivery efficiency and minimizing tumor proliferation risks.

Implementation Method 1

capable of specifically binding to CXCR4 and promoting the internalization of therapeutic agents into CXCR4-expressing cells

Methodology Applied

Scientific EffectReceptor-mediated endocytosis:

Implementation Method 2

facilitating endosomal escape and efficient delivery

Methodology Applied

Scientific EffectEndosomal escape:

Data Source

PatentUS11590198B2Methods and reagents for efficient and targeted delivery of therapeutic molecules to CXCR4 cells

Publication Date: 2023.02.28 CENT DE INVESTIGACION BIOMEDICA & RED & BIOING BIOMATERIALES Y NANOMEDICINA CIBER BBN

AI summary

Conjugates comprising a targeting moiety specific for the CXCR4 and based on the polyphemusin-derived peptide and a therapeutic or imaging agent are provided. Therapeutic and diagnostic methods with the conjugates which require specific targeting to CXCR4+cells are provided as well.