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The item below is very difficult and needs a great deal of thought. It is extracts from the full article. What it tells us is that the science of applying nanotechnology to medicine and the delivery of drugs is well on the way to mimicking the way a virus works in affecting the human body.
Clearly, if this can be done for a medicine intended to assist the body, it can be done with substances designed for another purpose. The difference is that for the most part, medicines are regulated, are obliged to be tested and there is supervision and examination of the effects.
As we know there is a vast range of household and personal products that do not have any of these safeguards and are produced almost regardless of the costs to health in both the short and long term.
Quote:
Virus-Inspired Design Principles of Nanoparticle-Based Bioagents
Hongyan Yuan, Changjin Huang, Sulin Zhang*
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, United States of America
ABSTRACT
The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.
Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation.
Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.
Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25–30 nm, and optimally several tens of ligands should be coated onto NPs.
These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.
In this article, we aim to establish guiding principles for the biomimetic design of NPs with high uptake rate, one of the key parameters that assess the efficacy of NP-based therapeutics.
Noting that correlating the biophysical parameters of NPs with the uptake rate may analytically be complex, we circumvent the difficulty by separately deriving the endocytic time of a single NP and the equilibrium cellular uptake when immersing the cell in a solution with dispersed NPs.
The endocytic time and cellular uptake together indicate the uptake rate. From thermodynamic analyses, we reveal that particle size and ligand density interrelatedly govern the uptake rate. The interrelated effects can be interpreted from a general framework of energy balance between NP-membrane adhesion and membrane deformation.
The interrelation suggests that tailoring only one design parameter may not be effective to achieve high uptake rate. We construct a phase diagram of the uptake rate in the space of particle size and ligand density, which may serve as a design map for NP-based therapeutics. Finally, we extend our discussions by including the effects of other relevant biophysical parameters.
Discussion
Through thermodynamic analyses, we revealed that the endocytic time of a single NP and the cellular uptake when immersing the cell into a solution with dispersed NPs are governed by the unified framework of energy balance between adhesion and membrane deformation.
We established phase diagrams in the space of particle size and ligand density for both the endocytic time and the cellular uptake. We identified from the phase diagrams the lower (upper) bounds below (beyond) which the endocytic time goes to infinite or the cellular uptake vanishes.
We further revealed that the mechanisms governing the lower and upper bounds of the endocytic time and the cellular uptake are the same: the lower bounds correspond to the enthalpic limit of the NP-membrane adhesion strength, while the upper bounds to the entropic limit.
The computed endocytic time and the cellular uptake allow us to define the uptake rate. It should be mentioned that the uptake rate defined here is different from what is typically measured in experiments [13] since the complex dynamics of receptor binding and debonding with NPs is not fully taken into account.
However, it may still serve as an important index to assess the uptake efficacy of NP-based therapeutics. The optimal size at which the uptake rate maximizes agrees with experimental data [8], [13], [14], [18]. Our model also predicts that, optimally several tens of ligands should be coated onto the NP surface in order to achieve high uptake rate.
These findings are supported both by the experimental data and the typical viral structures. The interrelated dependence of the uptake rate on the particle size and ligand density predicted by our analysis invites well-controlled experiments for further validation.
We further discussed the effects of other relevant biophysical parameters on the uptake rate, including the receptor density, the relative energy scale of ligand-receptor binding energy and membrane bending rigidity, membrane tension, and the bulk density of NPs. All the effects can be coherently interpreted by the variation of the enthalpic and entropic adhesion strength.
The phase diagram of the uptake rate in the space of particle size and ligand density thus serves as a design map that guides the rational designs of NP-based bioagents for biosensing [38], [39], bioimaging [40], [41], and drug delivery [42], [43].
Unquote.
Brilliant work, but only in the right hands for the right purpose.
Clearly, if this can be done for a medicine intended to assist the body, it can be done with substances designed for another purpose. The difference is that for the most part, medicines are regulated, are obliged to be tested and there is supervision and examination of the effects.
As we know there is a vast range of household and personal products that do not have any of these safeguards and are produced almost regardless of the costs to health in both the short and long term.
Quote:
Virus-Inspired Design Principles of Nanoparticle-Based Bioagents
Hongyan Yuan, Changjin Huang, Sulin Zhang*
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, United States of America
ABSTRACT
The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.
Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation.
Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.
Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25–30 nm, and optimally several tens of ligands should be coated onto NPs.
These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.
In this article, we aim to establish guiding principles for the biomimetic design of NPs with high uptake rate, one of the key parameters that assess the efficacy of NP-based therapeutics.
Noting that correlating the biophysical parameters of NPs with the uptake rate may analytically be complex, we circumvent the difficulty by separately deriving the endocytic time of a single NP and the equilibrium cellular uptake when immersing the cell in a solution with dispersed NPs.
The endocytic time and cellular uptake together indicate the uptake rate. From thermodynamic analyses, we reveal that particle size and ligand density interrelatedly govern the uptake rate. The interrelated effects can be interpreted from a general framework of energy balance between NP-membrane adhesion and membrane deformation.
The interrelation suggests that tailoring only one design parameter may not be effective to achieve high uptake rate. We construct a phase diagram of the uptake rate in the space of particle size and ligand density, which may serve as a design map for NP-based therapeutics. Finally, we extend our discussions by including the effects of other relevant biophysical parameters.
Discussion
Through thermodynamic analyses, we revealed that the endocytic time of a single NP and the cellular uptake when immersing the cell into a solution with dispersed NPs are governed by the unified framework of energy balance between adhesion and membrane deformation.
We established phase diagrams in the space of particle size and ligand density for both the endocytic time and the cellular uptake. We identified from the phase diagrams the lower (upper) bounds below (beyond) which the endocytic time goes to infinite or the cellular uptake vanishes.
We further revealed that the mechanisms governing the lower and upper bounds of the endocytic time and the cellular uptake are the same: the lower bounds correspond to the enthalpic limit of the NP-membrane adhesion strength, while the upper bounds to the entropic limit.
The computed endocytic time and the cellular uptake allow us to define the uptake rate. It should be mentioned that the uptake rate defined here is different from what is typically measured in experiments [13] since the complex dynamics of receptor binding and debonding with NPs is not fully taken into account.
However, it may still serve as an important index to assess the uptake efficacy of NP-based therapeutics. The optimal size at which the uptake rate maximizes agrees with experimental data [8], [13], [14], [18]. Our model also predicts that, optimally several tens of ligands should be coated onto the NP surface in order to achieve high uptake rate.
These findings are supported both by the experimental data and the typical viral structures. The interrelated dependence of the uptake rate on the particle size and ligand density predicted by our analysis invites well-controlled experiments for further validation.
We further discussed the effects of other relevant biophysical parameters on the uptake rate, including the receptor density, the relative energy scale of ligand-receptor binding energy and membrane bending rigidity, membrane tension, and the bulk density of NPs. All the effects can be coherently interpreted by the variation of the enthalpic and entropic adhesion strength.
The phase diagram of the uptake rate in the space of particle size and ligand density thus serves as a design map that guides the rational designs of NP-based bioagents for biosensing [38], [39], bioimaging [40], [41], and drug delivery [42], [43].
Unquote.
Brilliant work, but only in the right hands for the right purpose.
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