Covalent Polymer Network for Protein Delivery

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Solution Overview

Problem

Current methods for delivering proteins and biological macromolecules across cellular membranes face challenges such as instability, immunogenicity, and low loading capacities, particularly due to non-specific fouling and toxicities associated with electrostatic interactions and limited release control.

Innovation Solution

The development of polymer-protein conjugates where proteins are covalently conjugated to a polymer network, allowing for stable encapsulation and controlled release within cells in response to specific microenvironments, utilizing reactive side-chain functionalities and crosslinking to form a de-crosslinkable polymer network.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrostatic binding is used to attach proteins to polymers and nanoparticles, then protein delivery is achieved, but non-specific fouling and toxicities occur

Engineering Contradiction:

Improveprotein deliveryVSAvoidnon-specific fouling and toxicities

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the interaction mechanism from electrostatic (non-covalent) to covalent bonding, fundamentally altering the chemical parameter of the protein-polymer interaction. This transition eliminates non-specific fouling and toxicities associated with electrostatic interactions while maintaining reliable protein delivery and enabling controlled release through de-crosslinking

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite structure where proteins are covalently integrated into a polymer network through crosslinking. This composite material combines the stability of covalent bonds with the controlled degradability of the polymer matrix, achieving both reliable delivery and reduced harmful effects

Inventive Principle:

Principle #40Composite materials

2Object-affected harmful factors

If proteins are encapsulated in water-filled compartments such as liposomes, then fouling issues are addressed, but loading capacities are low

Engineering Contradiction:

Improvefouling issuesVSAvoidloading capacities

Core Design Contradiction:

Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent transitions from physical encapsulation (water-filled compartments) to covalent integration within a polymer network. This parameter change in the containment mechanism allows proteins to be firmly embedded in the polymer matrix, significantly increasing loading capacity while maintaining protection from fouling

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite polymer-protein network where proteins are covalently bound within the polymer structure. This composite approach provides both fouling protection and high loading capacity, as proteins are integrated into the bulk material rather than confined to aqueous compartments

Inventive Principle:

Principle #40Composite materials

3Reliability

If non-covalent self-assembly is used for protein delivery, then delivery is achieved, but reversibility and activity control are limited

Engineering Contradiction:

ImprovedeliveryVSAvoidreversibility and activity control

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces dynamic control through stimulus-responsive de-crosslinking. The covalent polymer network can be reversibly broken and reformed in response to specific stimuli (pH, redox conditions, enzymes), enabling controlled release and activity modulation while maintaining stable delivery

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The invention utilizes changes in chemical parameters (pH, redox state, enzyme presence) to trigger de-crosslinking and protein release. This parameter-based control provides versatile and reversible activity modulation while maintaining reliable delivery under physiological conditions

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 enables high-fidelity encapsulation and traceless release of proteins, maintaining structural and functional integrity, with improved stability and reduced toxicity, facilitating targeted delivery and activity within cells.

Implementation Method 1

the crosslinked polymer network is de-crosslinkable thereby releasing the protein

Methodology Applied

Scientific EffectDe-crosslinking:

Implementation Method 2

the polymer-protein conjugate is formed by one or more reactions between one or more side chain functionalities of the polymer and one or more surface-exposed functional groups of one or more lysine residues of the protein, leading to covalent capture and organization of the polymer around the protein

Methodology Applied

Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentUS11672867B2Protein-templated self-assembly of a covalent polymer network for intracellular trafficking and traceless release

Publication Date: 2023.06.13 UNIV OF MASSACHUSETTS

AI summary

The invention provides polymers and polymer-based nano-structures, in particular, polymers and polymer network to which biomolecules (e.g., proteins, antibodies, peptide aptamers) can be covalently conjugated and stably encapsulated therein and be controllably delivered and released upon degradation of the nano-structures in response to specific microenvironment, and compositions and methods of preparation and use thereof.