Ultrasmall Fluorescent Silica Nanoparticles Size Control
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Solution Overview
Problem
Current methods for synthesizing ultrasmall silica and aluminosilicate nanoparticles face challenges such as limited size control, aggregation issues due to PEGylation, low incorporation efficiencies of fluorescent dyes, especially near-infrared (NIR) emitters, and the lack of compositions other than silica for <10 nm sized fluorescent nanoparticles.
Innovation Solution
An aqueous synthesis methodology is developed to produce narrowly size-dispersed fluorescent silica and aluminosilicate nanoparticles with size control accuracy below 1 nm. This method allows for the covalent encapsulation of various fluorophores, including NIR emitters, and the addition of extra silica shells to enhance brightness. The use of an aluminum sol-gel precursor enables the synthesis of fluorescent aluminosilicate nanoparticles with improved encapsulation efficiency and brightness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If the Stöber process is used to synthesize silica nanoparticles, then particles with diameters from tens of nm to microns can be produced, but particle sizes of 10 nm and below are at the limit of size control due to reaction kinetics limitations in alcohol
Solution Approach 1:
The patent changes the solvent parameter from alcohol to water, and adjusts pH conditions to achieve precise size control below 10 nm. This parameter change enables the synthesis of ultrasmall particles (2-10 nm) with narrow size distribution that cannot be achieved with conventional alcohol-based Stöber process
2Reliability
If silica particle surfaces are covalently covered with PEG, then steric stability is improved, but loss of surface charge during PEGylation may result in particle aggregation or broadening of particle size distribution
Solution Approach 1:
The patent performs PEGylation during the particle formation process rather than as a subsequent step. This preliminary action allows for controlled surface modification while particles are still forming, preventing aggregation and maintaining narrow size distribution while achieving steric stability
3Quantity of substance
If silane-conjugated organic fluorescent dyes with negatively charged groups are encapsulated into SNPs, then fluorescent labeling is achieved, but covalent encapsulation efficiencies are low due to electrostatic repulsion between silica and fluorophore
Solution Approach 1:
The patent uses aluminum sol-gel precursors as intermediaries to facilitate fluorophore encapsulation. The aluminum species mediate the interaction between silica and fluorophore, enabling efficient covalent encapsulation of negatively charged NIR dyes that would otherwise be repelled by the silica surface
4Reliability
If particles greater than 12 nm are used, then sufficient brightness and stability are achieved, but they are not effectively cleared from the body in vivo and unfavorably distribute to the liver and other organs/tissues
Solution Approach 1:
The patent optimizes particle size parameters to fall within the 2-10 nm range, which enables renal clearance while maintaining sufficient fluorescence brightness. This parameter optimization resolves the trade-off between clearance efficiency and signal intensity that plagues larger particles
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 resulting nanoparticles exhibit quantum yields of approximately 0.8, approaching the theoretical brightness limit, and can be PEGylated for steric stability. These nanomaterials show potential for applications in nanomedicine, including cancer diagnostics and therapy, with tunable properties and enhanced performance characteristics.
Implementation Method 1
an aqueous synthesis methodology is developed to produce narrowly size-dispersed fluorescent silica and aluminosilicate nanoparticles
Implementation Method 2
This method allows for the covalent encapsulation of various fluorophores, including NIR emitters
Implementation Method 3
the addition of extra silica shells to enhance brightness
Implementation Method 4
These nanomaterials show potential for applications in nanomedicine, including cancer diagnostics and therapy, with tunable properties and enhanced performance characteristics
Data Source
AI summary
An aqueous synthesis methodology for the preparation of silica nanoparticles (SNPs), core-shell SNPs having, for example, a size of 2 to 15 nm and narrow size-dispersion with size control below 1 nm, i.e. at the level of a single atomic layer. Different types of dyes, including near infrared (NIR) emitters, can be covalently encapsulated within and brightness can be enhanced via addition of extra silica shells. The surface may be functionalized with polyethylene glycol (PEG) groups and, optionally, specific surface ligands. This aqueous synthesis methodology also enables synthesis of 2 to 15 nm sized fluorescent core and core-shell aluminosilicate nanoparticles (ASNPs) which may also be surface functionalized. Encapsulation efficiency and brightness of highly negatively charged NIR fluorophores is enhanced relative to the corresponding SNPs without aluminum.