Nanocomplexes of polyanion-modified proteins for intracellular delivery
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Solution Overview
Problem
Current protein-based therapeutic delivery systems face challenges in effectively transporting proteins into cells, particularly intracellular sites, due to the impermeability of the cell membrane, leading to inadequate therapeutic effects.
Innovation Solution
A nanocomplex comprising a lipid-like nanoparticle formed from a cationic lipid-based compound and a modified protein with an anionic polymer, which binds via non-covalent interaction to facilitate targeted and efficient intracellular delivery of proteins, with a particle size of 50 to 1000 nm, enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein-based therapeutics are used to target intracellular sites, then therapeutic efficacy is improved, but the cell membrane impermeability prevents effective delivery
Solution Approach 1:
The patent uses a cell-penetrating peptide (CPP) as an intermediary mediator between the protein therapeutic and the cell membrane. The CPP conjugate acts as a shuttle that facilitates the transport of the protein across the impermeable cell membrane, enabling intracellular delivery without compromising the protein's therapeutic function.
Solution Approach 2:
The invention creates a composite structure by chemically conjugating the cell-penetrating peptide to the protein therapeutic. This composite molecule combines the membrane-trans penetrating capability of the CPP with the therapeutic function of the protein, resolving the contradiction between membrane impermeability and delivery efficiency.
2Ease of operation
If general delivery systems are used, then delivery capability is improved, but protein release into cells is ineffective
Solution Approach 1:
The cell-penetrating peptide conjugate enables self-service delivery by utilizing the cell's own endocytic pathways and membrane transport mechanisms. The CPP portion of the conjugate interacts with cellular components to facilitate its own and the attached protein's entry into the cell, eliminating the need for external delivery apparatus.
3Ease of operation
If cell membrane impermeability is addressed, then intracellular delivery is improved, but targeted release at specific sites is compromised
Solution Approach 1:
The patent applies local quality by designing the CPP conjugate to interact specifically with certain cell membrane components or intracellular targets. The conjugate can be engineered to recognize and bind to specific receptors or structures at the target site, ensuring precise localized release of the protein therapeutic within the cell.
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 nanocomplex effectively transports proteins into cells, achieving therapeutic effects by releasing them at the target site, demonstrating improved delivery efficiency and targeted cancer therapy potential.
Implementation Method 1
The lipid-like nanoparticle binds to the modified protein via non-covalent interaction to form the nanocomplex
Implementation Method 2
a nanocomplex that effectively transports proteins into cells to exert therapeutic effects
Data Source
AI summary
A nanocomplex, 50 to 1000 nm in size, containing a lipid-like nanoparticle formed of a cationic lipid-based compound and a modified protein formed of a protein and an anionic polymer that includes a plurality of polar groups, the lipid-like nanoparticle and the modified protein being non-covalently bonded to each other. Also disclosed are a method of preparing the above-described nanocomplex and use thereof for treating a medical condition. Further disclosed is a pharmaceutical composition containing a nanocomplex.