Metal-Chelated Polyphenol Nanoparticles for Low-Toxicity Nucleic Acid Delivery
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Solution Overview
Problem
Current nanoparticle delivery systems for nucleic acid drugs, such as those using cationic lipids and ionizable lipids, suffer from cytotoxicity and immunogenicity, limiting their clinical application.
Innovation Solution
A metal-chelated polyphenol complex nanoparticle system is developed, comprising a polyphenol molecular moiety and a metal ion moiety connected by a coordination bond, with a particle aggregation-inhibiting conjugated lipid and non-cationic or non-ionizable lipids, to encapsulate and deliver nucleic acids without using cationic or ionizable lipids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cationic lipid or ionizable lipid is used in nanoparticle delivery systems for nucleic acid drugs, then the encapsulation efficiency and delivery capability are improved, but cytotoxicity and immunogenicity increase
Solution Approach 1:
The patent extracts and removes the cationic lipid component from the nanoparticle delivery system, replacing it with a metal-chelated polyphenol complex that does not rely on positive charge for nucleic acid encapsulation. This extraction eliminates the source of cytotoxicity and immunogenicity while maintaining delivery functionality through alternative mechanisms such as metal ion coordination and polyphenol interactions.
Solution Approach 2:
The patent changes the fundamental chemical parameters of the nanoparticle surface by introducing metal-chelated polyphenol complexes with specific metal ions (Fe3+, Al3+, Ca2+) that provide different interaction mechanisms with nucleic acids. This parameter change allows the system to achieve encapsulation without the harmful effects of cationic lipids, as the metal-chelated polyphenol complex interacts with negatively charged nucleic acids through coordination chemistry rather than electrostatic attraction.
2Reliability
If cationic lipid or ionizable lipid is used in nanoparticle delivery systems for nucleic acid drugs, then the transfection efficiency is improved, but immunogenicity increases
Solution Approach 1:
The patent removes the immunogenic cationic lipid component and replaces it with metal-chelated polyphenol complexes that do not trigger immune responses. The metal-chelated polyphenol complex maintains the ability to deliver nucleic acids into cells through alternative mechanisms, including metal ion-mediated endocytosis and polyphenol-facilitated membrane interaction, without the immunogenicity associated with cationic lipids.
Solution Approach 2:
The patent introduces metal-chelated polyphenol complex as an intermediary substance that mediates the delivery of nucleic acids into cells. This intermediary replaces the cationic lipid and provides the necessary functions for transfection through metal ion coordination and polyphenol interactions, while avoiding the immunogenicity of traditional cationic lipids.
3Ease of operation
If traditional lipid nanoparticles are used for delivering negatively charged drugs, then the delivery function is achieved, but toxicity remains high
Solution Approach 1:
The patent creates a composite nanoparticle system consisting of metal-chelated polyphenol complexes combined with conjugated lipids and other auxiliary components. This composite structure leverages the low toxicity of metal-chelated polyphenols, the membrane-interacting properties of conjugated lipids, and the functional capabilities of auxiliary components to achieve effective delivery without the high toxicity of traditional cationic lipid nanoparticles.
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 system reduces toxicity and improves biological safety, facilitating the delivery of negatively charged drugs like nucleic acids, with enhanced stability and effectiveness compared to traditional lipid nanoparticles.
Implementation Method 1
a metal-chelated polyphenol complex formed by a reaction of a polyphenol molecular moiety and a metal ion moiety, the polyphenol molecular moiety and the metal ion moiety being connected by a coordination bond
Implementation Method 2
The mechanism by which nanoparticles encapsulate nucleic acids is the adsorption of negatively charged nucleic acids by positively charged cationic lipid
Data Source
AI summary
The disclosure relates to the technical field of biological medicines, and particularly provides a metal-chelated polyphenol complex nanoparticle, a drug-lipid particle, preparation methods for the same, and the uses thereof. The present disclosure provides a metal-chelated polyphenol complex as a carrier for drugs for stability, delivery and the like, so that it interacts with other carriers to form a metal-chelated polyphenol complex nanoparticle for effective administration of negatively charged drug. High-efficiency systemic drug delivery can be achieved, while toxicity is significantly reduced compared to LNP containing cationic or ionizable lipids, enabling safe and effective treatment of diseases or disorders.