Selective Transport Molecule for Targeted Cargo Delivery
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Solution Overview
Problem
Current selective transport molecules face challenges with short plasma half-life, broad distribution, and slow washout from tissues, leading to non-specific uptake and limited therapeutic efficacy.
Innovation Solution
A selective transport molecule with the formula (A-X-B-C)-M or (A-X-B)-D, where A is a peptide with 5-9 consecutive acidic amino acids, B is a peptide with 5-20 consecutive basic amino acids, X is a linker, and M or D is a macromolecular carrier, designed for targeted delivery of therapeutic or imaging agents by cleaving the linker to facilitate cellular uptake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If selective transport molecules are used for targeted delivery, then therapeutic activity is improved, but plasma half-life is short and distribution is broad leading to non-specific uptake
Solution Approach 1:
The molecule is divided into distinct functional segments: a macromolecular carrier (M or D) for circulation, a peptide sequence (A-X-B) for targeted transport, and a cargo moiety (C) for therapeutic/imaging function. This segmentation allows each component to optimize its specific function while working together as a unified system.
Solution Approach 2:
The invention creates a composite molecular structure combining a macromolecular carrier (such as dendrimers or PEG polymers) with a specifically designed peptide sequence and cargo moiety. This composite structure integrates the long circulation half-life of the macromolecular carrier with the targeted cell uptake capability of the peptide sequence.
2Reliability
If selective transport molecules are used for targeted delivery, then therapeutic activity is improved, but washout from tissues is slow leading to non-specific uptake
Solution Approach 1:
The peptide sequence (A-X-B) provides dynamic control over the molecule's behavior: it maintains stability during circulation, enables active transport into target cells, and facilitates controlled release of cargo. The cleavable linker (X) adds another layer of dynamics by allowing protease-mediated release of the cargo moiety after cellular internalization.
Solution Approach 2:
The invention exploits parameter changes in different biological environments: the peptide sequence responds to protease presence, pH differences between extracellular and intracellular compartments, and cellular uptake mechanisms to transition from a circulation-optimized state to a delivery-optimized state, achieving fast washout from non-target tissues.
3Duration of action of moving object
If a macromolecular carrier is used to enhance circulation, then in vivo circulation is improved, but device complexity increases
Solution Approach 1:
The macromolecular carrier serves multiple functions simultaneously: it extends plasma half-life through reduced renal clearance, provides a platform for attaching the targeted peptide sequence, and can be designed with inherent biocompatibility and biodegradability. This multi-functionality reduces the need for additional separate components.
Solution Approach 2:
The peptide sequence (A-X-B) acts as an intermediary between the macromolecular carrier and the cargo moiety, facilitating controlled release and targeted delivery. The cleavable linker (X) specifically mediates the release of cargo upon protease cleavage, providing a simple yet effective mechanism that avoids complex release systems.
Data Source
AI summary
Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.