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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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Phase diagram of cellular uptake in the space of particle size and ligand density.
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pone-0013495-g004: Phase diagram of cellular uptake in the space of particle size and ligand density.

Mentions: Figure 4 plots the phase diagram of the cellular uptake in the space of particle radius and ligand density. This phase diagram is similar to that for the endocytic time in Fig. 2, indicating that the uptake behavior of these two cases shares the same mechanism. Based on Eqs. (7) and (13), the lower bounds of these two phase diagram are exactly the same. As the particle size and ligand density increase, increasingly more receptors diffuse toward the wrapping sites, and the receptors in the free membrane regions are nearly depleted, i.e., . Under this condition, the entropic penalty becomes significant and substantially lowers the adhesion strength. Corresponding to this entropic limit, an upper bound exists at which the cellular uptake vanishes.


Virus-inspired design principles of nanoparticle-based bioagents.

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

Phase diagram of cellular uptake in the space of particle size and ligand density.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0013495-g004: Phase diagram of cellular uptake in the space of particle size and ligand density.
Mentions: Figure 4 plots the phase diagram of the cellular uptake in the space of particle radius and ligand density. This phase diagram is similar to that for the endocytic time in Fig. 2, indicating that the uptake behavior of these two cases shares the same mechanism. Based on Eqs. (7) and (13), the lower bounds of these two phase diagram are exactly the same. As the particle size and ligand density increase, increasingly more receptors diffuse toward the wrapping sites, and the receptors in the free membrane regions are nearly depleted, i.e., . Under this condition, the entropic penalty becomes significant and substantially lowers the adhesion strength. Corresponding to this entropic limit, an upper bound exists at which the cellular uptake vanishes.

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