Stiffness can mediate balance between hydrodynamic forces and avidity to impact the targeting of flexible polymeric nanoparticles in flow

Farokhirad, Samaneh; Ranganathan, Abhay; Myerson, Jacob W.; Muzykantov, Vladimir R.; Ayyaswamy, P. S.; Eckmann, David M.; Radhakrishnan, Ravi

doi:10.1039/c8nr09594a

Cited by 18 publications

(29 citation statements)

References 41 publications

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“…Similarly, the effects of agents inducing exocytosis on the uptake of drug delivery systems may vary depending on the nanocarrier type, surface characteristics, targeting moieties, and drug cargo. For instance, the carrier composition, surface charge, stiffness, etc., can modulate cell interaction, uptake, and trafficking (Howard et al, 2014;Merkel et al, 2012;Muro, 2012a;Farokhirad et al, 2019). Yet, this varies for different targets: e.g., polystyrene, poly(lactic-co-glycolic acid), and DNA-built nanocarriers targeting ICAM-1 showed relatively similar binding and uptake in cell culture and biodistribution in mice (Muro et al, 2006a;Muro, 2014;Garnacho et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

δ-Tocopherol Effect on Endocytosis and Its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: A New Type of Drug Interaction?

Manthe

Rappaport

Long

et al. 2019

J Pharmacol Exp Ther

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Induction of lysosomal exocytosis alleviates lysosomal storage of undigested metabolites in cell models of lysosomal disorders (LDs). However, whether this strategy affects other vesicular compartments, e.g., those involved in endocytosis, is unknown. This is important both to predict side effects and to use this strategy in combination with therapies that require endocytosis for intracellular delivery, such as lysosomal enzyme replacement therapy (ERT). We investigated this using d-tocopherol as a model previously shown to induce lysosomal exocytosis and cell models of type A Niemann-Pick disease, a LD characterized by acid sphingomyelinase (ASM) deficiency and sphingomyelin storage. d-Tocopherol and derivative CF3-T reduced net accumulation of fluid phase, ligands, and polymer particles via phagocytic, caveolae-, clathrin-, and cell adhesion molecule (CAM)-mediated pathways, yet the latter route was less affected due to receptor overexpression. In agreement, d-tocopherol lowered uptake of recombinant ASM by deficient cells (known to occur via the clathrin pathway) and via targeting intercellular adhesion molecule-1 (associated to the CAM pathway). However, the net enzyme activity delivered and lysosomal storage attenuation were greater via the latter route. Data suggest stimulation of exocytosis by tocopherols is not specific of lysosomes and affects endocytic cargo. However, this effect was transient and became unnoticeable several hours after tocopherol removal. Therefore, induction of exocytosis in combination with therapies requiring endocytic uptake, such as ERT, may represent a new type of drug interaction, yet this strategy could be valuable if properly timed for minimal interference.

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Section: Discussionmentioning

confidence: 99%

δ-Tocopherol Effect on Endocytosis and Its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: A New Type of Drug Interaction?

Manthe

Rappaport

Long

et al. 2019

J Pharmacol Exp Ther

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“…The trajectories and interactions between the coarse-grained molecules are calculated using the stochastic differential equation (Eq. 26) which is integrated forward in time, allowing for the study of the temporal evolution and the dynamics of complex fluids, such as polymers [69–71] and colloids.…”

Section: Computational Methods and Implementationmentioning

confidence: 99%

“…Specifically, on the hydrodynamic front, the shear, confinement, and interaction with HCT will collectively define the shape of the flexible NP, which through shape-dependent hydrodynamic interactions will impact NP spatial distribution and margination. On the adhesive front, upon multivalent binding, the entropy loss per receptor-ligand bond model is lower for the flexible NP compared to its rigid counterpart, thereby driving larger multivalency [71]. However, an additional contribution to entropy loss resulting from a change in accessible conformations of NP upon binding applies for the flexible NP, which is absent for the rigid NP [71].…”

Section: Illustrative Examples Of Nanofluid Studies and Select Applicmentioning

confidence: 99%

“…On the adhesive front, upon multivalent binding, the entropy loss per receptor-ligand bond model is lower for the flexible NP compared to its rigid counterpart, thereby driving larger multivalency [71]. However, an additional contribution to entropy loss resulting from a change in accessible conformations of NP upon binding applies for the flexible NP, which is absent for the rigid NP [71]. The cumulative effects of these entropic contributions will compensate with the enthalpy of multivalent binding leading to new rules for NP binding [71].…”

Section: Illustrative Examples Of Nanofluid Studies and Select Applicmentioning

confidence: 99%

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Nanoparticle transport phenomena in confined flows

Radhakrishnan

Farokhirad

Eckmann

et al. 2019

Advances in Heat Transfer

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Nanoparticles submerged in confined flow fields occur in several technological applications involving heat and mass transfer in nanoscale systems. Describing the transport with nanoparticles in confined flows poses additional challenges due to the coupling between the thermal effects and fluid forces. Here, we focus on the relevant literature related to Brownian motion, hydrodynamic interactions and transport associated with nanoparticles in confined flows. We review the literature on the several techniques that are based on the principles of non-equilibrium statistical mechanics and computational fluid dynamics in order to simultaneously preserve the fluctuation-dissipation relationship and the prevailing hydrodynamic correlations. Through a review of select examples, we discuss the treatments of the temporal dynamics from the colloidal scales to the molecular scales pertaining to nanoscale fluid dynamics and heat transfer. As evident from this review, there, indeed has been little progress made in regard to the accurate modeling of heat transport in nanofluids flowing in confined geometries such as tubes. Therefore the associated mechanisms with such processes remain unexplained. This review has revealed that the information available in open literature on the transport properties of nanofluids is often contradictory and confusing. It has been very difficult to draw definitive conclusions. The quality of work reported on this topic is non-uniform. A significant portion of this review pertains to the treatment of the fluid dynamic aspects of the nanoparticle transport problem. By simultaneously treating the energy transport in ways discussed in this review as related to momentum transport, the ultimate goal of understanding nanoscale heat transport in confined flows may be achieved.

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“…These disparate hydrodynamic fields and molecular forces can be integrated into a single GLE to realize a unified description of particle dynamics under the influence of molecular and hydrodynamic forces [85]. Another approach to integrating these forces is via the Fokker Planck approach using the sequential multiscale method paradigm [131].…”

Section: (Eq 21)mentioning

confidence: 99%

Multiscale modeling: foundations, historical milestones, current status, and future prospects

Radhakrishnan¹

2020

Preprint

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Research problems in the domains of physical, engineering, biological sciences, often span multiple time and length scales, owing to the complexity of information transfer underlying mechanisms. Multiscale modeling (MSM) and high-performance computing (HPC) have emerged as indispensable tools for tackling such complex problems. We review the foundations, historical developments, and current paradigms in MSM. A paradigm shift in MSM implementations is being fueled by the rapid advances and emerging paradigms in HPC at the dawn of exascale computing. Moreover, amidst the explosion of data science, engineering, and medicine, machine learning (ML) integrated with MSM is poised to enhance the capabilities of standard MSM approaches significantly, particularly in the face of increasing problem complexity. The potential to blend MSM, HPC, and ML presents opportunities for unbound innovation and promises to represent the future of MSM and explainable ML that will likely define the fields in the 21st century.

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Stiffness can mediate balance between hydrodynamic forces and avidity to impact the targeting of flexible polymeric nanoparticles in flow

Abstract: Computational investigations of deformable polymeric nanoparticles under flow and adhesive environment.

Cited by 18 publications

References 41 publications

δ-Tocopherol Effect on Endocytosis and Its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: A New Type of Drug Interaction?

δ-Tocopherol Effect on Endocytosis and Its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: A New Type of Drug Interaction?

Nanoparticle transport phenomena in confined flows

Multiscale modeling: foundations, historical milestones, current status, and future prospects

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