Protein-Templated Covalent Polymer Network for Intracellular 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 success in achieving controlled and targeted release.
Innovation Solution
A covalent self-assembly approach where proteins are templated to form a polymer network, allowing for high-fidelity encapsulation and traceless release within cells by reacting side chain functionalities of polymers with surface-exposed lysine residues, using a disulfide-based linker that responds to reducing intracellular environments for controlled protein release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If electrostatic binding of proteins to complementarily charged polymers and nanoparticles is used, then protein delivery is achieved, but non-specific fouling and toxicities occur
Solution Approach 1:
The patent uses a disulfide-based self-immolative linker as an intermediary between the polymer and protein. This linker enables controlled covalent attachment while allowing traceless release under reducing intracellular conditions, thereby achieving reliable protein delivery without the non-specific fouling and toxicities associated with electrostatic binding methods
2Object-affected harmful factors
If encapsulation of proteins in water-filled compartments such as liposomes is used, then fouling issues are addressed, but loading capacities are low
Solution Approach 1:
The patent employs a composite polymer system consisting of a disulfide-based self-immolative linker combined with a polymer backbone. This composite material provides both the protective encapsulation environment that prevents fouling and the high loading capacity needed to achieve effective protein delivery, overcoming the limitations of liposomal encapsulation
3Stability of the object's composition
If covalent conjugation of polymers to proteins is used, then stable encapsulation is achieved, but controlled and targeted release is difficult
Solution Approach 1:
The patent utilizes parameter changes in the chemical environment, specifically the redox state, to control release. The disulfide-based self-immolative linker remains stable under oxidizing extracellular conditions, providing stable encapsulation, but undergoes cleavage under reducing intracellular conditions, enabling controlled and targeted protein release without requiring complex external stimuli
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 strategy enables stable protein delivery with high loading capacity, protection from protease degradation, and efficient release within the cytosol, maintaining protein structure and function, and is applicable to a broad range of proteins, demonstrating improved efficacy over existing methods.
Implementation Method 1
using a disulfide-based linker that responds to reducing intracellular environments for controlled protein release
Implementation Method 2
A covalent self-assembly approach where proteins are templated to form a polymer network
Implementation Method 3
reacting side chain functionalities of polymers with surface-exposed lysine residues
Data Source
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.