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.

Nanoparticles (NPs) are emerging as promising carrier platforms for targeted drug delivery and imaging probes. To evaluate the delivery efficiency, it is important to predict the distribution of NPs within blood vessels. NP size, shape and vessel geometry are believed to influence its biodistribution in circulation. Whereas, the effect of size on nanoparticle distribution has been extensively studied, little is known about the shape and vessel geometry effect. This paper describes a computational model for NP transport and distribution in a mimetic branched blood vessel using combined NP Brownian dynamics and continuum fluid mechanics approaches. The simulation results indicate that NPs with smaller size and rod shape have higher binding capabilities as a result of smaller drag force and larger contact area. The binding dynamics of rod-shaped NPs is found to be dependent on their initial contact points and orientations to the wall. Higher concentration of NPs is observed in the bifurcation area compared to the straight section of the branched vessel. Moreover, it is found that Péclet number plays an important role in determining the fraction of NPs deposited in the branched region and the straight section. Simulation results also indicate that NP binding decreases with increased shear rate. Dynamic NP re-distribution from low to high shear rates is observed due to the non-uniform shear stress distribution over the branched channel. This study would provide valuable information for NP distribution in a complex vascular network.

Nanomedicine is a promising application of nanotechnology in medicine, which can drastically improve drug delivery efficiency through targeted delivery. However, characterization of the nanoparticle targeted delivery process under vascular environment is very challenging due to the small scale of nanoparticles and the complex in vivo vascular system. To understand such complicated system, various computational models are developed to help reveal nanoparticle targeted delivery process and design nanoparticles for optimal delivery. This article discusses a few computational tools to model the nanoparticle delivery process and design nanoparticles for efficient targeted delivery. The modeling approaches span from continuum vascular flow, particle Brownian adhesion dynamics, to molecular level ligand-receptor binding. Computer simulation is envisioned to be able to optimize drug carrier design and predict drug delivery efficiency for patient specific vascular environment.

We have designed a potential drug delivery system by combining low-molecular-weight heparin to iron oxide magnetic nanoparticles with an average size of 20 nm. The particles were synthesized by the NaBH4 reduction of FeCl2 and then coated with poly-L-lysine. Heparin was noncovalently conjugated on these nanoparticles via the interactions between the negatively charged sulfate and carboxylate groups of heparin and the positively charged amine group of poly-L-lysine. The nanoparticles were examined by using transmission electron microscopy, x-ray diffraction, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, and zeta potential measurements. The data provide direct evidence that the heparin was immobilized at the surface of poly-L-lysine-coated iron oxide nanoparticles. Magnetic measurements revealed the particles are ferromagnetic with a saturation magnetization of 31 emu/g.

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