scholarly journals Quantifying and controlling bond multivalency for advanced nanoparticle targeting to cells

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Elliot Y. Makhani ◽  
Ailin Zhang ◽  
Jered B. Haun

AbstractNanoparticles have drawn intense interest as delivery agents for diagnosing and treating various cancers. Much of the early success was driven by passive targeting mechanisms such as the enhanced permeability and retention (EPR) effect, but this has failed to lead to the expected clinical successes. Active targeting involves binding interactions between the nanoparticle and cancer cells, which promotes tumor cell-specific accumulation and internalization. Furthermore, nanoparticles are large enough to facilitate multiple bond formation, which can improve adhesive properties substantially in comparison to the single bond case. While multivalent binding is universally believed to be an attribute of nanoparticles, it is a complex process that is still poorly understood and difficult to control. In this review, we will first discuss experimental studies that have elucidated roles for parameters such as nanoparticle size and shape, targeting ligand and target receptor densities, and monovalent binding kinetics on multivalent nanoparticle adhesion efficiency and cellular internalization. Although such experimental studies are very insightful, information is limited and confounded by numerous differences across experimental systems. Thus, we focus the second part of the review on theoretical aspects of binding, including kinetics, biomechanics, and transport physics. Finally, we discuss various computational and simulation studies of nanoparticle adhesion, including advanced treatments that compare directly to experimental results. Future work will ideally continue to combine experimental data and advanced computational studies to extend our knowledge of multivalent adhesion, as well as design the most powerful nanoparticle-based agents to treat cancer.

2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.


Plants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1261
Author(s):  
Robin Lardon ◽  
Danny Geelen

Plant regeneration is essential for survival upon wounding and is, hence, considered to be a strong natural selective trait. The capacity of plant tissues to regenerate in vitro, however, varies substantially between and within species and depends on the applied incubation conditions. Insight into the genetic factors underlying this variation may help to improve numerous biotechnological applications that exploit in vitro regeneration. Here, we review the state of the art on the molecular framework of de novo shoot organogenesis from root explants in Arabidopsis, which is a complex process controlled by multiple quantitative trait loci of various effect sizes. Two types of factors are distinguished that contribute to natural regenerative variation: master regulators that are conserved in all experimental systems (e.g., WUSCHEL and related homeobox genes) and conditional regulators whose relative role depends on the explant and the incubation settings. We further elaborate on epigenetic variation and protocol variables that likely contribute to differential explant responsivity within species and conclude that in vitro shoot organogenesis occurs at the intersection between (epi) genetics, endogenous hormone levels, and environmental influences.


Coatings ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 350 ◽  
Author(s):  
Andrey Pepelyshev ◽  
Feodor Borodich ◽  
Boris Galanov ◽  
Elena Gorb ◽  
Stanislav Gorb

Adhesion between rough surfaces is an active field of research where both experimental studies and theoretical modelling are used. However, it is rather difficult to conduct precise experimental evaluations of adhesive properties of the so-called anti-adhesive materials. Hence, it was suggested earlier by Purtov et al. (2013) to prepare epoxy resin replicas of surfaces having different topography and conduct depth-sensing indentation of the samples using a micro-force tester with a spherical smooth probe made of the compliant polydimethylsiloxane polymer in order to compare values of the force of adhesion to the surfaces. Surprising experimental observations were obtained in which a surface having very small roughness showed the greater value of the force of adhesion than the value for a replica of smooth surface. A plausible explanation of the data was given suggesting that these rough surfaces had full adhesive contact and their true contact area is greater than the area for a smooth surface, while the surfaces with higher values of roughness do not have full contact. Here, the experimental results of surface topography measurements and the statistical analysis of the data are presented. Several modern tests of normality used showed that the height distribution of the surfaces under investigation is normal (Gaussian) and hence the classic statistical models of adhesive contact between rough surfaces may formally be used. Employing one of the Galanov (2011) models of adhesive contact between rough surfaces, the plausible explanation of the experimental observations has been confirmed and theoretically justified.


Parasitology ◽  
2009 ◽  
Vol 136 (14) ◽  
pp. 1935-1942 ◽  
Author(s):  
F. TRIPET

SUMMARYThere has been a recent shift in the literature on mosquito/Plasmodium interactions with an increasingly large number of theoretical and experimental studies focusing on their population biology and evolutionary processes. Ecological immunology of mosquito-malaria interactions – the study of the mechanisms and function of mosquito immune responses to Plasmodium in their ecological and evolutionary context – is particularly important for our understanding of malaria transmission and how to control it. Indeed, describing the processes that create and maintain variation in mosquito immune responses and parasite virulence in natural populations may be as important to this endeavor as describing the immune responses themselves. For historical reasons, Ecological Immunology still largely relies on studies based on non-natural model systems. There are many reasons why current research should favour studies conducted closer to the field and more realistic experimental systems whenever possible. As a result, a number of researchers have raised concerns over the use of artificial host-parasite associations to generate inferences about population-level processes. Here I discuss and review several lines of evidence that, I believe, best illustrate and summarize the limitations of inferences generated using non-natural model systems.


2019 ◽  
Vol 116 (6) ◽  
pp. 1968-1973 ◽  
Author(s):  
Yue Sun ◽  
Feng Ding ◽  
Zhixuan Zhou ◽  
Chonglu Li ◽  
Maoping Pu ◽  
...  

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0–1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.


2020 ◽  
Author(s):  
Mie Ichihara

<p>In the earth and planetary sciences, the term "analog experiment" indicates laboratory experiments that use analog materials to investigate natural processes. Scaled experiments constitute a representative sub-category of analog experiments. They are designed to have the same dominant dimensionless parameter in the same range as the targeted natural processes. Other primary uses of analog experiments are education and outreach. Reproducing similar phenomena in front of the audience is useful in explaining the essence of the complex dynamics of natural processes. However, it is often the case that we do not fully understand the physics of the experimental systems or the targeted natural phenomena. In such cases, especially when the process is complex, it is difficult to guarantee the scaling similarity. When we take such laboratory phenomena as a research subject of earth science, we encounter critical comments about the scaling issue.</p><p>Nevertheless, I think it scientifically important to consider questions like follows. What is the mechanism of the experimental phenomena? Why the behaviors of the experiment look similar to the natural phenomena? To what extent the laboratory and the natural systems are similar. To indicate experimental studies to elucidate these questions, I would like to define "analogy experiment" as a new sub-category of analog experiments.  Some recent experiments are presented as examples.</p>


Author(s):  
Agata Wronska ◽  
Jacek Andres ◽  
Tomasz Altamer ◽  
Agata Dudek ◽  
Robert Ulewicz

The Friction stir welding (FSW) is a complex process, depending on many factors: machine, clamping device, material and tools. Parameters that have a direct impact on the quality of the joint include the rotational speed, welding speed, clamping force, geometry and tool plunging depth. The paper presents the results of experimental studies concerning the effect of tool pin length on the microstructure and mechanical strength of joints of thin sheets made of Al 7075 alloy. A tool with an adjustable pin with concave shoulder was used to weld the joints. Different pin lengths were used, which were selected with respect to the thickness of the welded joint. The specimens were subjected to visual evaluation, metallographic tests and mechanical strength testing. The results indicate that the pin length has a decisive effect on the microstructural changes in the joint and thus influencing the strength of the FSW joints.


2021 ◽  
Vol 845 (1) ◽  
pp. 012126
Author(s):  
R I Lee ◽  
Yu N Rizaeva ◽  
D N Psarev ◽  
M R Kiba ◽  
A N Bykonya ◽  
...  

Abstract Due to the high specific surface area of nanoparticles, in comparison with micro-sized particles, a significant improvement in the consumer properties of polymer nanocomposites is achieved at relatively low concentrations of nanoscale fillers (up to 5%). Research and subsequent development of new polymer nanocomposites are of great scientific and practical interest, as they provide further development of promising high-performance technologies for restoring landing holes, increasing the post-repair life of basic parts and reliability and significantly reducing the cost of repairing agricultural machinery. The article describes the influence of metal nanoparticles on the thermophysical and mechanical properties of elastomers, presents the results of experimental studies of the deformation-strength and adhesive properties of a nanocomposite based on F-40 elastomer filled with nanoscale copper and aluminum particles as well as its optimal composition. Comparative data on the heat and heat resistance of the F - 40 elastomer and the nanocomposite based on it are presented.


2014 ◽  
Vol 14 (2) ◽  
pp. 1399-1442 ◽  
Author(s):  
R. J. Herbert ◽  
B. J. Murray ◽  
T. F. Whale ◽  
S. J. Dobbie ◽  
J. D. Atkinson

Abstract. In order to understand the impact of ice formation in clouds, a quantitative understanding of ice nucleation is required, along with an accurate and efficient representation for use in cloud resolving models. Ice nucleation by atmospherically relevant particle types is complicated by inter-particle variability in nucleating ability, as well as a stochastic, time-dependent, nature inherent to nucleation. Here we present a new and computationally efficient Framework for Reconciling Observable Stochastic Time-dependence (FROST) in immersion mode ice nucleation. This framework is underpinned by the finding that the temperature dependence of the nucleation rate coefficient controls the residence-time and cooling-rate dependence of freezing. It is shown that this framework can be used to reconcile experimental data obtained on different time scales with different experimental systems, and it also provides a simple way of representing the complexities of ice nucleation in cloud resolving models. The routine testing and reporting of time-dependent behaviour in future experimental studies is recommended, along with the practice of presenting normalised datasets following the methods outlined here.


2019 ◽  
Vol 44 (2) ◽  
pp. 26-30
Author(s):  
Bojan Petrović ◽  
Evgenija Marković ◽  
Tamara Perić ◽  
Sanja Kojić

Changes in composition and new material characteristics require verification in clinical and experimental studies. Investigating glass-ionomer cements under laboratory conditions encounters problems in interpreting the results and in comparing them with other types of materials tested in the same way. As the connection between the glass-ionomer cements and the dental tissues is delicate, it is often the case that the impact of fractures and other artifacts is either underestimated or over-dimensioned when interpreting the results. A critical review was performed, with defining the main problems regarding the usage of SEM, EDX and nanoindentation techniques in glass-ionomer based materials evaluation.


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