Multivalent Nanoprobes for Nucleic Acid Scavenging
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Solution Overview
Problem
Current nucleic acid binding technologies, such as monovalent fluorochromes and large nanoparticle-based agents, are ineffective in suppressing immune responses and imaging nucleic acids due to low affinity, rapid clearance, and poor tissue penetration, limiting their therapeutic and diagnostic potential in managing tissue damage from injuries and infections.
Innovation Solution
Development of multivalent nucleic acid binding nanoprobes comprising vital fluorochromes connected to a polymer, optimized for size and valency, which bind to nucleic acids, reducing immune stimulation and enabling effective imaging and therapeutic intervention at injury sites.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If monovalent fluorochromes are used, then the structure is simple, but the affinity for nucleic acids is low and clearance is rapid
Solution Approach 1:
The patent combines multiple fluorochrome units (2-20 copies) with a polymer backbone to create a multivalent nanoprobe. This merging of multiple binding units onto a single carrier molecule dramatically increases the overall affinity for nucleic acids while maintaining a manageable structural complexity through modular design.
Solution Approach 2:
The invention creates a composite nanoprobe structure combining fluorochrome units with a polymer matrix. This composite approach allows optimization of both binding affinity (through multiple fluorochrome units) and pharmacokinetic properties (through polymer selection), resolving the contradiction between simplicity and reliability.
2Quantity of substance
If large nanoparticle-based agents are used, then the nucleic acid binding capacity is high, but tissue penetration is poor and circulation half-life is short
Solution Approach 1:
The patent optimizes critical parameters including nanoprobe size (4-10 nm diameter), molecular weight (40-1000 kDa), and fluorochrome-to-polymer ratio (2-20 copies). These parameter adjustments enable the nanoprobe to maintain high binding capacity while achieving optimal tissue penetration and circulation characteristics.
Solution Approach 2:
The invention concentrates multiple fluorochrome units at specific binding sites on the nanoprobe surface, creating localized high-affinity binding regions. This local concentration strategy maximizes nucleic acid binding capacity without requiring the entire nanoprobe structure to be large, thereby preserving tissue penetration ability.
3Reliability
If the number of fluorochromes per polymer is increased, then the nucleic acid binding affinity is improved, but the nanoprobe size and molecular weight increase
Solution Approach 1:
The patent employs a range of fluorochrome copies (2-20) that provides more than enough binding sites to achieve saturating affinity for nucleic acids. This partial excess action ensures high binding reliability while avoiding the need for excessive numbers of fluorochromes that would unnecessarily increase molecular weight and size.
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 nanoprobes effectively scavenge nucleic acids, attenuate immune responses, and provide diagnostic imaging, reducing tissue damage and inflammation, with enhanced affinity and circulation half-life, compared to existing technologies.
Implementation Method 1
Vital fluorochromes are generally positively charged. The positive charge assists in preventing the VFs from passing through intact membranes and binding to nucleic acids in healthy cells. The rings intercalate between the bases of double-stranded DNA and thus, is able to bind to nucleic acid with high affinity.
Implementation Method 2
Vital fluorochromes (VF) are generally low molecular weight organic compounds... The rings intercalate between the bases of double-stranded DNA and thus, is able to bind to nucleic acid with high affinity. The fluorochrome can be used to detect and image nucleic acids.
Data Source
AI summary
The present disclosure provides nucleic acid binding nanoprobes having one or more fluorochromes and a polymer, where each of the fluorochromes is connected to the polymer, and methods of using the same.