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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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Schematics of receptor-mediated endocytosis of NPs.
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pone-0013495-g003: Schematics of receptor-mediated endocytosis of NPs.

Mentions: We next analyze the cellular uptake of NPs when immersing the cell in a solution with dispersed NPs of bulk density . Driven by the chemical potential difference between the adherent and suspended NPs, the many-NP-cell system reaches a thermodynamic equilibrium with a steady-state cellular uptake, as suggested by a set of prior experiments [12], [13], [14]. We assume that in the thermodynamic equilibrium, a certain number of NPs, N, are wrapped by cell membrane with different degrees of wrapping [19], [30]; some are internalized, as shown in Fig. 3. At the thermodynamic equilibrium, the membrane is partitioned into two parts: a free, planar membrane region of area and a curved membrane region of area bound to the NPs. Receptors in the planar membrane region with a density are diffusible, while those in the curved membrane region with a density of are densely packed on the NP surfaces via ligand-receptor binding. Denoting by the number of NPs whose wrapped area is k, one follows and [30]. The balance of the receptor potentials in the free and bound membrane regions gives rise to (Methods: system free energy of multiple NP-membrane interaction)(9)One notes the close similarity of Eqs. (3) and (9). The chemical potential balance of the NPs in the bulk solution and on the cell membrane gives rise to a Boltzmann wrapping size distribution, as(10)where is naturally defined as the adhesion strength, where the subscript “M” stands for the case of multiple NPs interacting with the cell membrane, and(11)The approximation in Eq. (11) holds because the last term is much smaller than the other two terms. The cellular uptake is the number of particles that are fully wrapped, i.e., . Conservation of the receptors yields:(12)Combining Eqs. (9)–(12), one finds the equilibrium densities of bound and free receptors and the wrapping-size distribution, and therefore the cellular uptake .


Virus-inspired design principles of nanoparticle-based bioagents.

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

Schematics of receptor-mediated endocytosis of NPs.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0013495-g003: Schematics of receptor-mediated endocytosis of NPs.
Mentions: We next analyze the cellular uptake of NPs when immersing the cell in a solution with dispersed NPs of bulk density . Driven by the chemical potential difference between the adherent and suspended NPs, the many-NP-cell system reaches a thermodynamic equilibrium with a steady-state cellular uptake, as suggested by a set of prior experiments [12], [13], [14]. We assume that in the thermodynamic equilibrium, a certain number of NPs, N, are wrapped by cell membrane with different degrees of wrapping [19], [30]; some are internalized, as shown in Fig. 3. At the thermodynamic equilibrium, the membrane is partitioned into two parts: a free, planar membrane region of area and a curved membrane region of area bound to the NPs. Receptors in the planar membrane region with a density are diffusible, while those in the curved membrane region with a density of are densely packed on the NP surfaces via ligand-receptor binding. Denoting by the number of NPs whose wrapped area is k, one follows and [30]. The balance of the receptor potentials in the free and bound membrane regions gives rise to (Methods: system free energy of multiple NP-membrane interaction)(9)One notes the close similarity of Eqs. (3) and (9). The chemical potential balance of the NPs in the bulk solution and on the cell membrane gives rise to a Boltzmann wrapping size distribution, as(10)where is naturally defined as the adhesion strength, where the subscript “M” stands for the case of multiple NPs interacting with the cell membrane, and(11)The approximation in Eq. (11) holds because the last term is much smaller than the other two terms. The cellular uptake is the number of particles that are fully wrapped, i.e., . Conservation of the receptors yields:(12)Combining Eqs. (9)–(12), one finds the equilibrium densities of bound and free receptors and the wrapping-size distribution, and therefore the cellular uptake .

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