Nanoparticle Drug Carriers via Protein Corona Engineering
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Solution Overview
Problem
Nanoparticle-based therapeutics face challenges in targeting transformed cells due to uncontrolled protein corona interactions and lack of systematic approaches in drug carrier development, leading to inefficiencies in drug delivery.
Innovation Solution
A novel process combining high-throughput shotgun-based proteomics and bioinformatics to control nanoparticle-protein interactions, leveraging the protein corona for site-specific targeting of cancer cells by isolating and analyzing the protein corona using liquid chromatography tandem mass spectrometry and data mining, followed by antibody conjugation and passive adsorption of siRNA onto graphene or graphene oxide nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional nanoparticle formulations are used, then the nanoparticle can be synthesized with desired properties, but uncontrolled protein corona formation masks the synthetic identity and impedes targeted delivery
Solution Approach 1:
The patent applies preliminary action by pre-coating nanoparticle surfaces with specific proteins (such as apolipoproteins) before administration. This pre-established protein corona ensures that the nanoparticle presents the correct biological identity to target cells, preventing uncontrolled protein adsorption from masking the intended targeting moieties. The systematic approach involves selecting proteins that bind to both the nanoparticle surface and target cell receptors, thereby ensuring reliable targeted delivery.
Solution Approach 2:
The patent converts the harmful effect of protein corona formation into a beneficial feature by deliberately engineering the protein corona composition. Instead of trying to prevent protein adsorption, the method harnesses the natural tendency of proteins to adsorb onto nanoparticle surfaces and directs this process toward forming a controlled, functional corona that enhances targeted delivery. This involves selecting proteins with specific binding properties that facilitate cell uptake and targeted transport.
2Productivity
If researchers mix and match components based on theoretical knowledge, then drug carrier configurations can be developed quickly, but the lack of systematic methodology results in wasted time, money, and resources on ineffective configurations
Solution Approach 1:
The patent applies parameter changes by systematically varying and optimizing key parameters in nanoparticle formulation, including surface charge, hydrophobicity, size, and protein coating composition. This systematic parameter optimization allows researchers to identify the most effective configurations for targeted delivery, reducing the need to test numerous ineffective combinations. The method establishes structure-activity relationships that guide future formulation development.
Solution Approach 2:
The patent implements feedback mechanisms through in vitro and in vivo evaluation of nanoparticle formulations to assess their targeting efficiency and cellular uptake. This feedback information is used to iteratively optimize the nanoparticle design, refining the protein corona composition and nanoparticle properties based on actual performance data. The systematic evaluation process identifies which configurations work effectively and which should be avoided in future development.
3Object-generated harmful factors
If PEGylation or zwitterionic coatings are applied to impede protein adsorption, then some protein corona formation is reduced, but sufficient protein adsorption still occurs to form a corona layer that masks the synthetic identity
Solution Approach 1:
The patent converts the harmful effect of protein corona formation into a beneficial feature by deliberately engineering the protein corona composition. Instead of trying to prevent protein adsorption, the method harnesses the natural tendency of proteins to adsorb onto nanoparticle surfaces and directs this process toward forming a controlled, functional corona that enhances targeted delivery. This involves selecting proteins with specific binding properties that facilitate cell uptake and targeted transport.
Solution Approach 2:
The patent applies preliminary action by pre-coating nanoparticle surfaces with specific proteins (such as apolipoproteins) before administration. This pre-established protein corona ensures that the nanoparticle presents the correct biological identity to target cells, preventing uncontrolled protein adsorption from masking the intended targeting moieties. The systematic approach involves selecting proteins that bind to both the nanoparticle surface and target cell receptors, thereby ensuring reliable targeted delivery.
4Reliability
If high-throughput shotgun-based proteomics and bioinformatics are implemented, then systematic control of nanoparticle-protein interactions is achieved, but the process complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the complex nanoparticle formulation process into distinct, manageable stages: (1) nanoparticle synthesis with controlled surface properties, (2) systematic protein corona formation under defined conditions, (3) high-throughput proteomics analysis to identify corona proteins, (4) bioinformatics analysis to predict targeting efficiency, and (5) iterative optimization based on results. This segmented approach makes the complex process more controllable and reproducible.
Solution Approach 2:
The patent uses bioinformatics algorithms as an intermediary between the experimental data from proteomics and the nanoparticle formulation decisions. The bioinformatics tools analyze the complex proteomics data to identify proteins with desirable targeting properties, translating raw data into actionable formulation guidance. This intermediary layer simplifies the interpretation of complex data and guides systematic optimization without requiring direct manual analysis of all proteomics results.
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 process enables efficient and cost-effective site-specific targeting of cancer cells, outperforming conventional gold standards for intracellular drug delivery and is universally applicable to various nanoparticle types and therapeutic payloads.
Implementation Method 1
a large subset of which adsorb onto the drug and change essentially all of its synthetic properties including size, dispersion, aggregation state, bio-targeting ability
Implementation Method 2
each corona isolate is analyzed using liquid chromatography tandem mass spectrometry on the nano-scale (nano LC-MS) for profiling the identity and quantity of the adsorbed proteins
Implementation Method 3
followed by repeated centrifugation for isolation and washing of the corona layer
Implementation Method 4
An antibody against the outputted 'best' corona protein is then functionalized onto the outputted 'best' nanoparticle formulation via conventional EDC-NHS crosslinking
Implementation Method 5
A therapeutic payload, consisting of siRNA against the BCl2 oncogene, is then adsorbed onto the nanoparticle formulation via a simple mixing process via passive adsorption
Data Source
AI summary
The invention relates to the method for building nanoparticle-based drug carriers and the nanoparticle based drug delivery system able to manipulate the corresponding protein corona for specific and potent drug delivery to cancer cells.