Modeling Particle Shape-Dependent Dynamics in Nanomedicine

Abstract

One of the major challenges in nanomedicine is to improve nanoparticle cell selectivity and adhesion efficiency through designing functionalized nanoparticles of controlled sizes, shapes, and material compositions. Recent data on cylindrically shaped filomicelles are beginning to show that non-spherical particles remarkably improved the biological properties over spherical counterpart. Despite these exciting advances, non-spherical particles have not been widely used in nanomedicine applications due to the lack of fundamental understanding of shape effect on targeting efficiency. This paper intends to investigate the shape-dependent adhesion kinetics of non-spherical nanoparticles through computational modeling. The ligand-receptor binding kinetics is coupled with Brownian dynamics to study the dynamic delivery process of nanorods under various vascular flow conditions. The influences of nanoparticle shape, ligand density, and shear rate on adhesion probability are studied. Nanorods are observed to contact and adhere to the wall much easier than their spherical counterparts under the same configuration due to their tumbling motion. The binding probability of a nanorod under a shear rate of 8 s −1 is found to be three times higher than that of a nanosphere with the same volume. The particle binding probability decreases with increased flow shear rate and channel height. The Brownian motion is found to largely enhance nanoparticle binding. Results from this study contribute to the fundamental understanding and knowledge on how particle shape affects the transport and targeting efficiency of nanocarriers, which will provide mechanistic insights on the design of shape-specific nanomedicine for targeted drug delivery applications.

Green Synthesis and Characterization of Silver Nanoparticles from Crocus Mathewii; A Disremembered Turkish Flowering Plant

“…It has been observed that AgNPs synthesized from plant extracts are formed in various sizes; mostly 10-100 nm average particle size (APS). Shah et al also reviewed the nanoparticles as nanomedicines [43] . Zhao et al synthesized graphene oxide (GO)/AgNPs/luminol composites with electrochemiluminescence activity for sensitive detection of DNA methyltransferase activity with the APS of 18 nm [44] .…”

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms

“…Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8-12). These particles, inspired by the diverse, evolutionarily conserved shapes of pathogens and cells, are being used to study the role of carrier shape on cellular internalization, in vivo transport, and organ distribution (6,11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).Despite these pioneering studies, there remains a significant knowledge gap in our fundamental understanding of the interplay between nanoscale shape and size on cellular internalization, especially for clinically relevant polymer-based hydrophilic nanoparticles. Most in vivo drug delivery and imaging applications have proposed the use of nanoparticles with hydrophilic "stealth" surfaces [often achieved through poly(ethylene glycol) (PEG)-based surface modifications] as well as neutral to anionic surface charge, primarily to allow longer in vivo circulation time by reducing protein adsorption and rapid clearance by the reticuloendothelial system (2, 24-27).…”

“…Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8-12). These particles, inspired by the diverse, evolutionarily conserved shapes of pathogens and cells, are being used to study the role of carrier shape on cellular internalization, in vivo transport, and organ distribution (6,11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Controlling the morphology of copolymeric vectors for next generation nanomedicine

“…As has been already stated the effect of NV morphology upon its performance in vivo depends upon its ability to permeate various tissues and perform well in the bloodstream, so that it can circulate freely whilst being capable of interacting with its environment and, in particular, vascular tissues. It has been shown from modelling the flow characteristics of elongated particles that they would, in the bloodstream, naturally drift towards the vessel walls and thereby be more suitable for targeting applications due to this intelligent behaviour [18,81,82]. In other work, rod-shaped particles have shown greater transport across intestinal cells compared to their spherical counterparts, both with active targeting (via biotinylation) enhancing their accumulation at the desired cells, laying the foundation for their development towards oral drug delivery applications; however, development of biodegradable NVs that display such morphology is imperative [15].…”