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Virus-inspired design principles of nanoparticle-based bioagents.

Yuan H, Huang C, Zhang S - PLoS ONE (2010)

Bottom Line: The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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Related in: MedlinePlus

Schematics of endocytosis of a single NP.The membrane is partitioned into three regions due to the wrapping: the bound region of area , the impacted region of area , and the remote region of area .
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pone-0013495-g001: Schematics of endocytosis of a single NP.The membrane is partitioned into three regions due to the wrapping: the bound region of area , the impacted region of area , and the remote region of area .

Mentions: Similar to crack extension or healing in a crystal lattice [25], [26], [27], the discrete wrapping of an NP by cell membrane undergoes a series of local energy minima, for which thermodynamics applies at different degrees of wrapping. We consider a single spherical NP of radius R being wrapped by cell membrane, as shown in Fig. 1. Wrapping partitions the membrane into three distinct regions: a small region of area bound with the NP, an impacted region of area in the vicinity of the bound region, and a remote region for the rest of cell membrane, where M is the total membrane area. We consider a general stage of wrapping characterized by the degree of wrapping . Concentrating of receptors onto the NP surface rapidly depletes the receptors in the region i.e., , where is the receptor density in the area . The balance of receptor potentials in the bound and impacted regions gives rise to (Methods: system free energy of single NP-membrane interaction)(3)where . The pressure balance between the bound and impacted regions yields(4)At specified wrapping extent, and can be obtained by solving Eqs. (3) and (4), yielding the distribution of the receptors.


Virus-inspired design principles of nanoparticle-based bioagents.

Yuan H, Huang C, Zhang S - PLoS ONE (2010)

Schematics of endocytosis of a single NP.The membrane is partitioned into three regions due to the wrapping: the bound region of area , the impacted region of area , and the remote region of area .
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957438&req=5

pone-0013495-g001: Schematics of endocytosis of a single NP.The membrane is partitioned into three regions due to the wrapping: the bound region of area , the impacted region of area , and the remote region of area .
Mentions: Similar to crack extension or healing in a crystal lattice [25], [26], [27], the discrete wrapping of an NP by cell membrane undergoes a series of local energy minima, for which thermodynamics applies at different degrees of wrapping. We consider a single spherical NP of radius R being wrapped by cell membrane, as shown in Fig. 1. Wrapping partitions the membrane into three distinct regions: a small region of area bound with the NP, an impacted region of area in the vicinity of the bound region, and a remote region for the rest of cell membrane, where M is the total membrane area. We consider a general stage of wrapping characterized by the degree of wrapping . Concentrating of receptors onto the NP surface rapidly depletes the receptors in the region i.e., , where is the receptor density in the area . The balance of receptor potentials in the bound and impacted regions gives rise to (Methods: system free energy of single NP-membrane interaction)(3)where . The pressure balance between the bound and impacted regions yields(4)At specified wrapping extent, and can be obtained by solving Eqs. (3) and (4), yielding the distribution of the receptors.

Bottom Line: The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics.Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus