This paper describes how branch lengths of anisotropic nanoparticles can affect interactions between grafted ligands and cell-membrane receptors. Using live-cell, single-particle tracking, we found that DNA aptamer-gold nanostar nanoconstructs with longer branches showed improved binding efficacy to human epidermal growth factor receptor 2 (HER2) on cancer cell membranes. Inhibiting nanoconstruct-HER2 binding promoted nonspecific interactions, which increased the rotational speed of long-branched nanoconstructs but did not affect that of short-branched constructs. Bivariate analysis of the rotational and translational dynamics showed that longer branch lengths increased the ratio of targeting to nontargeting interactions. We also found that longer branches increased the nanoconstruct-cell interaction times before internalization and decreased intracellular trafficking velocities. Differences in binding efficacy revealed by single-particle dynamics can be attributed to the distinct protein corona distributions on short- and long-branched nanoconstructs, as validated by transmission electron microscopy. Minimal protein adsorption at the high positive curvature tips of long-branched nanoconstructs facilitated binding of DNA aptamer ligands to HER2. Our study reveals the significance of nanoparticle branch length in regulating local chemical environment and interactions with live cells at the single-particle level.

We investigated the effect of nanoparticle (NP) image broadening and its contrast change dependence on a support matrix thickness in a transmission electron microscope (TEM). We measured the effect of NP size and atomic number on its image broadening. Based on the experimental TEM images we generated tomograms of NPs on four types of support matrix. The measured shape aspect ratio of the NPs in such tomograms depends on the geometry of the support matrix. For example, the aspect ratio of 6 nm NP placed on a thin film with window-frame support is 1.14, while the aspect ratio of 6 nm NP on a rod-shaped support with 910 nm diameter is 1.67 in a tomogram.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curvature and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spherical nanoparticles and to traditional microparticle technologies. Additionally, the anisotropic nanoparticle artificial antigen presenting cells efficiently engage with and activate T cells, ultimately leading to a marked anti-tumor effect in a mouse melanoma model that their spherical counterparts were unable to achieve. STATEMENT OF SIGNIFICANCE: Artificial antigen presenting cells (aAPC) can activate antigen-specific CD8+ T cells but have largely been limited to microparticle-based platforms and ex vivo T cell expansion. Although more amenable to in vivo use, nanoscale aAPC have traditionally been ineffective due to limited surface area available for T cell interaction. In this work, we engineered non-spherical biodegradable nanoscale aAPC to investigate the role of particle geometry and develop a translatable platform for T cell activation. The non-spherical aAPC developed here have increased surface area and a flatter surface for T cell engagement and, therefore, can more effectively stimulate antigen-specific T cells, resulting in anti-tumor efficacy in a mouse melanoma model.

Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis among children worldwide, yet there is no vaccine for RSV disease. This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles (CNP) to modulate reactive oxygen (ROS) and nitrogen (RNS) species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo. Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods, respectively. Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential. In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages. Specifically, cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels. Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFα and IL-12p70, while simultaneously decreasing M2 CD206 expression. Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice. Notably, cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation, avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils, which are associated with RSV-mediated inflammation. In conclusion, we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.

In this paper, two novel micro heat sinks (MHSs) were designed and subjected to thermal analysis using a numerical method. The fluid used was Boehmite alumina-water nanofluid (NFs) with high volume fractions (VOFs). Studies were conducted to determine the influence of a variety of nanoparticle (NP) shapes, such as platelet brick, blade, cylinder, and Os. The heatsink (HS) was made of copper, and the NFs entered it through the middle and exited via four outlets at the side of the HS. The finite element method was used to simulate the NFs flow and heat transfer in the HSs. For this purpose, Multi Physics COMSOL software was used. The maximum and middle values of HS temperature (T-MAX and T-Mid), thermal resistance (TH-R), heat transfer coefficient (h), FOM, etc., were studied for different NP shapes, and with Reynolds numbers (Re) of 300, 1000, and 1700, and VOFs of 0, 3, and 6%. One of the important outcomes of this work was the better thermal efficiency of the HS with rectangular fins. Moreover, it was discovered that a rise in Re increased the heat transfer. In general, adding NPs with high VOFs to MHSs is not appropriate in terms of heat. The Os shape was the best NP shape, and the platelet shape was the worst NP shape for high NPVOF. When NPs were added to an MHS, the temperature of the MHS dropped by an average of 2.8 or 2.19 K, depending on the form of the pin-fins contained inside the MHS (circular or square). The addition of NPs in the MHS with circular and square pin-fins enhanced the pressure drop by 13.5% and 13.3%, respectively, when the Re = 1700.

Unlike in the bulk, at the nanoscale shape dictates properties. The imperative to understand and predict nanocrystal shape led to the development, over several decades, of a large number of mathematical models and, later, their software implementations. In this review, the various mathematical approaches used to model crystal shapes are first overviewed, from the century-old Wulff construction to the year-old (2020) approach to describe supported twinned nanocrystals, together with a discussion and disambiguation of the terminology. Then, the multitude of published software implementations of these Wulff-based shape models are described in detail, describing their technical aspects, advantages and limitations. Finally, a discussion of the scientific applications of shape models to either predict shape or use shape to deduce thermodynamic and/or kinetic parameters is offered, followed by a conclusion. This review provides a guide for scientists looking to model crystal shape in a field where ever-increasingly complex crystal shapes and compositions are required to fulfil the exciting promises of nanotechnology.

Numerical studies were performed to estimate the heat transfer and hydrodynamic properties of a forced convection turbulent flow using three-dimensional horizontal concentric annuli. This paper applied the standard k-ε turbulence model for the flow range 1 × 104 ≤ Re ≥ 24 × 103. A wide range of parameters like different nanomaterials (Al2O3, CuO, SiO2 and ZnO), different particle nanoshapes (spherical, cylindrical, blades, platelets and bricks), different heat flux ratio (HFR) (0, 0.5, 1 and 2) and different aspect ratios (AR) (1.5, 2, 2.5 and 3) were examined. Also, the effect of inner cylinder rotation was discussed. An experiment was conducted out using a field-emission scanning electron microscope (FE-SEM) to characterize metallic oxides in spherical morphologies. Nano-platelet particles showed the best enhancements in heat transfer properties, followed by nano-cylinders, nano-bricks, nano-blades, and nano-spheres. The maximum heat transfer enhancement was found in SiO2, followed by ZnO, CuO, and Al2O3, in that order. Meanwhile, the effect of the HFR parameter was insignificant. At Re = 24,000, the inner wall rotation enhanced the heat transfer about 47.94%, 43.03%, 42.06% and 39.79% for SiO2, ZnO, CuO and Al2O3, respectively. Moreover, the AR of 2.5 presented the higher heat transfer improvement followed by 3, 2, and 1.5.

A thermal analysis of Cu-CuO/ blood nanofluids flow in asymmetric microchannel propagating with wave velocity is presented in this study. For the blood, a micropolar fluid model is considered to investigate the microrotation effects of blood flow. Thermal radiation effects and the influence of nanoparticle shape, electric double layer thickness, and electromagnetic fields on the flow are studied. Three types of nanoparticles shapes namely cylinder, bricks and platelets are taken into account. Governing equations are solved under the approximations of long wavelength, low Reynolds number, and Debye-Hückel linearization. Numerical computations are performed for the axial pressure gradient, axial velocity, spin velocity and temperature distribution. The effects of various physical parameters on flow and thermal characteristics are computed and their physical interpretation is also discussed. The outcomes indicate that the axial velocity of Cu-CuO/blood nanoparticles strongly depends on applied electromagnetic field and microrotation. The model\'s finding will be applicable in designing the smart electromagnetic micro pumps for the hemodialysis and lungs-on-chip devices for the pumping of the blood.

Nanoparticles have become an important utility in many areas of medical treatment such as targeted drug and treatment delivery as well as imaging and diagnostics. These advances require a complete understanding of nanoparticles\' fate once placed in the body. Upon exposure to blood, proteins adsorb onto the nanoparticles surface and form a protein corona, which determines the particles\' biological fate. This study reports on the protein corona formation from blood serum and plasma on spherical and rod-shaped nanoparticles. These two types of mesoporous silica nanoparticles have identical chemistry, porosity, surface potential, and size in the y-dimension, one being a sphere and the other a rod shape. The results show a significantly larger amount of protein attaching from both plasma and serum on the rod-like particles compared to the spheres. Interrogation of the protein corona by liquid chromatography-mass spectrometry reveals shape-dependent differences in the adsorption of immunoglobulins and albumin proteins from both plasma and serum. This study points to the need for taking nanoparticle shape into consideration because it can have a significant impact on the fate and therapeutic potential of nanoparticles when placed in the body.