Cross-linked Copolymer Complexes for Gene Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current gene therapy and protein/peptide drug delivery systems face challenges such as high cytotoxicity of cationic polymers, poor stability, and limited efficiency due to enzymatic degradation and cellular uptake barriers, which hinder effective transfection and delivery of nucleic acids and therapeutic molecules.
Innovation Solution
Development of cross-linked copolymers comprising alternating units of amino acid hydrazides and dialdehydes with PEG groups, forming imine and acylhydrazone bonds, which stabilize complexes in saline solutions while allowing acidic pH-induced degradation for efficient cellular delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cationic polymers (e.g., PEI) are used for gene delivery, then transfection efficiency is improved, but cytotoxicity increases
Solution Approach 1:
The invention changes the chemical parameters of the polymer by using dynamically reversible bonds (imine and acylhydrazone) instead of permanent covalent bonds. This allows the polymer to be stable at physiological pH for efficient transfection but degrade at acidic pH to reduce cytotoxicity, thus resolving the contradiction between transfection efficiency and cytotoxicity
Solution Approach 2:
The invention introduces dynamic reversibility into the polymer structure through pH-responsive imine and acylhydrazone bonds. The polymer transitions from a stable state at physiological pH (enabling high transfection efficiency) to a degradable state at acidic pH (reducing cytotoxicity), dynamically adapting to different environmental conditions to resolve the toxicity-efficiency contradiction
2Productivity
If nucleic acids are delivered into physiological environment, then gene therapy is achieved, but enzymatic degradation by nucleases occurs
Solution Approach 1:
The dynamically reversible polymer acts as an intermediary carrier that protects nucleic acids from nuclease degradation in the physiological environment while enabling controlled release at the target site through pH-responsive degradation, thus resolving the contradiction between delivery efficiency and nucleic acid stability
3Reliability
If cross-linked copolymers with PEG groups are used, then stability in saline solutions is improved, but complex structure increases
Solution Approach 1:
The invention creates a composite polymer structure combining amino acid hydrazides, dialdehydes with PEG groups, and dynamically reversible bonds. This composite structure integrates multiple functions (stability, biocompatibility, pH-responsiveness) into a single system, resolving the contradiction between enhanced stability and structural complexity
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 polymer-cargo-complexes demonstrate reduced cytotoxicity, enhanced stability, and efficient transfection and delivery of nucleic acids and peptides, with improved biocompatibility and biofunctionality, overcoming the limitations of existing systems.
Implementation Method 1
cross-linked copolymers comprising alternating units A and B forming a repeat unit A-B such that the copolymer comprises a (A-B)n backbone... unit A is a derivative of an amino acid hydrazide and unit B is a derivate of a dialdehyde... the copolymer comprises imine groups and acylhydrazone groups alternatingly linking together the alternating units A and B
Implementation Method 2
cargo molecules bound to the copolymers by electrostatic interactions... cargo molecules bound to the cross-linked copolymer by electrostatic interactions between the cargo molecules and the amino acid side chains of unit A
Data Source
AI summary
Polymer-cargo-complexes including cross-linked copolymers and cargo molecules bound to the copolymers by electrostatic interactions. The non-medical use thereof for transfection and to a kit including such polymer-cargo-complexes. The polymer-cargo-complexes for use in therapy, in particular for use in gene therapy or peptide/protein drug delivery. A method of preparing the polymer-cargo-complexes. A kit for preparing a polymer-cargo-complex of the invention.