Bioreversible Boronates for Cellular Cargo Delivery
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Solution Overview
Problem
Current methods for cellular delivery of biologic drugs face inefficiencies due to poor cellular uptake, biological instability, and immunogenicity, with existing strategies like cationic peptides and polymers showing limited success in overcoming these challenges.
Innovation Solution
The use of phenylboronic acid groups to enhance cellular uptake by forming covalent bonds with cargo molecules, such as nucleic acids, peptides, and proteins, facilitating their delivery into mammalian cells through interaction with cell-surface glycans, and providing a mechanism for potential release of the cargo within endosomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cationic peptides or polymers are used to enhance cellular delivery, then attraction to anionic cell surface is improved, but biological instability and immunogenicity worsen
Solution Approach 1:
The invention changes the chemical parameter of the delivery agent from cationic to boronic acid functional groups. Boronic acids form reversible covalent bonds with diols on cell surface glycans, providing stable yet biodegradable attachment that avoids the immunogenicity issues of cationic polymers while maintaining delivery efficiency
Solution Approach 2:
The invention creates a composite delivery system where the cargo molecule is conjugated to boronic acid groups, forming a hybrid structure that combines the stability of covalent bonding with the biocompatibility of natural boron-containing compounds found in human physiology
2Reliability
If cationic peptides or polymers are used to enhance cellular delivery, then attraction to anionic cell surface is improved, but immunogenicity worsens
Solution Approach 1:
The invention changes the chemical parameter of the delivery agent from cationic to boronic acid functional groups. Boronic acids form reversible covalent bonds with diols on cell surface glycans, providing stable yet biodegradable attachment that avoids the immunogenicity issues of cationic polymers while maintaining delivery efficiency
Solution Approach 2:
The boronic acid-cargo conjugate is designed as a temporary, biodegradable delivery vehicle that performs its function and then degrades into harmless natural metabolites, avoiding the persistent immunogenic response associated with synthetic cationic polymers
3Quantity of substance
If large complex assemblies with PBA are used for delivery, then cargo transport capability is improved, but device complexity worsens
Solution Approach 1:
The invention extracts the essential delivery function from large complex assemblies and reduces it to simple boronic acid functional groups attached directly to the cargo molecule. This minimalist approach maintains transport capability while eliminating the complexity of large polymeric or particulate delivery vehicles
Solution Approach 2:
Instead of using large assemblies throughout the entire cargo, the invention applies boronic acid groups locally at specific attachment points on the cargo molecule, providing sufficient delivery capability with minimal added 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
This approach significantly enhances the cellular uptake of cargo molecules, maintaining their biological activity and enabling efficient delivery of therapeutic agents like anticancer drugs and nucleic acids into cells, with the potential for controlled release within cellular compartments.
Implementation Method 1
Boronic acids readily form boronate esters with the 1,2- and 1,3-diols of saccharides
Implementation Method 2
The boronate ester linkages are susceptible to hydrolysis by intracellular esterases, thereby providing a mechanism for release of the cargo
Data Source
AI summary
Methods for enhancing cellular uptake of cargo molecules by boronating the cargo molecule, particularly with one or more phenylboronic acid groups. Boronation reagents for reversible boronation of cargo molecules, particularly, cargo molecules having one or more amino groups are provided.