Haemodynamic-dependent arrest of circulating tumour cells at large blood vessel bifurcations as new model for metastasis

Homing of circulating tumour cells (CTC) at distant sites represents a critical event in metastasis dissemination. In addition to physical entrapment, probably responsible of the majority of the homing events, the vascular system provides with geometrical factors that govern the flow biomechanics and impact on the fate of the CTC. Here we mathematically explored the distribution of velocities and the corresponding streamlines at the bifurcations of large blood vessel and characterized an area of low-velocity at the carina of bifurcation that favours the residence of CTC. In addition to this fluid physics effect, the adhesive capabilities of the CTC provide with a biological competitive advantage resulting in a marginal but systematic arrest as evidenced by dynamic in vitro recirculation in Y-microchannels and by perfusion in in vivo mice models. Our results also demonstrate that viscosity, as a main determinant of the Reynolds number that define flow biomechanics, may be modulated to limit or impair CTC accumulation at the bifurcation of blood vessels, in agreement with the apparent positive effect observed in the clinical setting by anticoagulants in advanced oncology disease.

Preparation and Physicochemical Characterization of Water-Soluble Pyrazole-Based Nanoparticles by Dendrimer Encapsulation of an Insoluble Bioactive Pyrazole Derivative

2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4) was synthetized and successfully evaluated concerning numerous biological activities, except for antimicrobial and cytotoxic effects. Due to the antimicrobial effects possessed by pyrazole nucleus, which have been widely reported, and the worldwide need for new antimicrobial agents, we thought it would be interesting to test BBB4 and to evaluate its possible antibacterial effects. Nevertheless, since it is water-insoluble, the future clinical application of BBB4 will remain utopic unless water-soluble BBB4 formulations are developed. To this end, before implementing biological evaluations, BBB4 was herein re-synthetized and characterized, and a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants. The obtained BBB4 nanoparticles (BBB4-G4K NPs) showed good drug loading (DL%), satisfying encapsulation efficiency (EE%), and a biphasic quantitative release profile governed by first-order kinetics after 24 h. Additionally, BBB4-G4K was characterized by ATR-FTIR spectroscopy, NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While, before the nanotechnological manipulation, BBB4 was completely water-insoluble, in the form of BBB4-G4K NPs, its water-solubility resulted in being 105-fold higher than that of the pristine form, thus establishing the feasibility of its clinical application.

Synthesis Polyelectrolyte Complex Membrane Polystyrene Sufonate-Chitosan from Styrofoam Waste as The Adsorbent for Cu(II) and Ni(II) Metal

ABSTRAK Telah dilakukan sintesis membran polistirena sulfonat (PSS)-kitosan dari modifikasi limbah styrofoam, kemudian dipelajari kemampuannya dalam mengadsorpsi logam Ni(II) dan Cu(II). Telah ditentukan pula komposisi optimum PSS-kitosan, uji stabilitas asam basa, dan kemampuan swellingnya. Parameter kajian adsorpsi yang dipelajari dalam penelitian ini meliputi pH optimum, kinetika adsorpsi, isoterm adsorpsi, pengaruh kation lain secara selektifitas, dan penentuan mekanisme adsorpsi. Analisis logam Cu(II) dan Ni(II) sebelum dan sesudah proses adsorpsi dilakukan dengan menggunakan metode Spektrofotometri Serapan Atom (SSA) Hasil penelitian menunjukkan bahwa polistirena sulfonat (PSS) berhasil diperoleh dari reaksi sulfonasi limbah styrofoam yang ditunjukan dengan spektra FTIR. Komposisi optimum membran PSS:kitosan untuk mengadsorpsi logam Cu(II) dan Ni(II) adalah perbandingan 60:40 dengan kestabilan, sifat fisik, dan kemampuan adsorpsi yang paling baik. Keadaan pH optimum adsorpsi logam Cu(II) dan Ni(II) berada pada pH 5, waktu optimum berturut-turut 45 menit dan 60 menit, serta konsentrasi optimum berturut-turut 60 ppm dan 40 ppm. Model kinetika dan isoterm adsorpsi logam Cu(II) dan Ni(II) pada membran PSS-kitosan adalah orde kedua semu (McKay dan Ho) dan model isoterm Freundlich. Tetapan laju reaksi logam Cu(II) dan Ni(II) pada pH 5 berturut-turut 0,480 mmol/g-1menit-1 dan 0,423 mmol/g-1menit-1. Adanya logam Ni(II) dalam adsorpsi Cu(II) tidak memberikan pengaruh yang signifikan sampai pada perbandingan Ni(II)/Cu(II)= 2:1, namun sebaliknya dengan kehadiran logam Cu(II) pada adsorpsi logam Ni(II) sudah memberikan pengaruh pada perbandingan Ni(II)/Cu(II)=1:1. Afinitas membran PSS-kitosan terhadap logam adalah Cu(II) > Ni(II). Pada studi desorpsi diketahui jenis interaksi antara adsorbat dan situs aktif adsorben merupakan mekanisme pembentukan kompleks, pemerangkapan dan pembentukan ikatan hidrogen. ABSTRACT Synthesis of polystyrene sulphonate (PSS) – chitosan membrane of styrofoam waste modification and its ability to adsorb Ni (II) and Cu (II) metals has been studied. The optimum composition of PSS-chitosan, acidity stability test, and swelling ability have been determined. The parameters of the adsorption study studied in this study include optimum pH, adsorption kinetics, adsorption isotherms, selective cationic effects, and determination of adsorption mechanisms. Analysis of Cu (II) and Ni (II) metals before and after the adsorption process was performed using Atomic Absorption Spectrophotometric (AAS) The results showed that polystyrene sulphonate (PSS) was obtained from the sulfonation of styrofoam waste using the FTIR spectra. The optimum composition of rasio PSS: chitosan membrane for adsorbing Cu (II) and Ni (II) is 60:40 with the best stability, physical properties, and adsorption capability. The optimum pH adsorption of Cu (II) and Ni (II) metals was at pH 5, the optimum time was 45 min and 60 min, and the optimum concentrations were 60 ppm and 40 ppm. The kinetic and adsorption models of Cu (II) and Ni (II) metals on PSS-chitosan membranes are second-order (McKay and Ho) and Freundlich isotherm model. The reaction rates of Cu (II) and Ni (II) reactions at pH 5 were 0.480 mmol / g-1menit-1 and 0.423 mmol / g-1menit-1. The presence of Ni (II) metal in Cu (II) adsorption did not give a significant effect to the ratio of Ni (II) / Cu (II) = 2: 1, but with the presence of Cu (II) metal on metal adsorption Ni (II) have an effect on the ratio of Ni (II) / Cu (II) = 1: 1. The affinity of PSS-chitosan membrane to metal is Cu (II)> Ni (II). Sequential desorption studies showed that the adsorption of Cu (II) and Ni (II) metals on the PSS-chitosan membrane were estimated to follow a complex formation, hydrogen bond formation, and physical entrapment mechanisms.

Comparative study on the physical entrapment of soy and mushroom proteins on the durability of bacterial cellulose bio‐leather

This study aimed to develop eco-friendly bacterial cellulose (BC) bio-leather with improved durability using plant-based proteins, namely soy protein isolate (SPI) and mushroom protein (MP), which were physically entrapped inside the BC, respectively. The amounts of the plant-based proteins were determined by evaluating the tensile strength of BC bio-leather, and were found to be 20 wt% and 50 wt% of BC for SPI and MP, respectively. The enhanced properties of mechanical strength and durability of BC bio-leather were measured in terms of changes in water resistance, tensile strength, flexibility, crease recovery, and dimensional stability. The durability of BC was improved after the entrapment of proteins, and moreover, the durability of BC entrapped with plant-based proteins was further improved by the addition of glycerol. Especially, BC entrapped with MP and glycerol had better water resistance, tensile strength, flexibility, and crease recovery compared to cowhide leather. The chemical and physical structures of BC bio-leathers were studied using Fourier transform-infrared spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, and energy dispersive X-ray spectroscopy analyses. From the results, it was confirmed that BC entrapped with MP and glycerol could be a suitable leather substitute.

Xeno-Hybrid Bone Graft Releasing Biomimetic Proteins Promotes Osteogenic Differentiation of hMSCs

Bone defect is a noteworthy health problem and is the second most transplanted tissue after blood. Numerous bone grafts are designed and applied in clinics. Limitations, however, from different aspects still exist, including limited supply, mechanical strength, and bioactivity. In this study, two biomimetic peptides (P2 and P6) are incorporated into a composite bioactive xeno hybrid bone graft named SmartBonePep®, with the aim to increase the bioactivity of the bone graft. The results, which include cytotoxicity, proliferation rate, confocal microscopy, gene expression, and protein qualification, successfully prove that the SmartBonePep® has multi-modal biological effects on human mesenchymal stem cells from bone marrow. The effective physical entrapment of P6 into a composite xeno-hybrid bone graft, withstanding manufacturing processes including exposure to strong organic solvents and ethylene oxide sterilization, increases the osteogenic potential of the stem cells as well as cell attachment and proliferation. P2 and P6 both show a strong biological potential and may be future candidates for enhancing the clinical performance of bone grafts.

Tuning Functional Behavior of Humic Acids through Interactions with Stöber Silica Nanoparticles

Humic acids (HA) exhibit fascinating multifunctional features, yet degradation phenomena as well as poor stability in aqueous environments strongly limit their use. Inorganic nanoparticles are emerging as a powerful interface for the development of robust HA bio-hybrid materials with enhanced chemical stability and tunable properties. Hybrid organic-inorganic SiO2/HA nanostructures were synthesized via an in-situ sol-gel route, exploiting both physical entrapment and chemical coupling. The latter was achieved through amide bond formation between carboxyl groups of HA and the amino group of 3-aminopropyltriethoxysilane (APTS), as confirmed by Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Monodisperse hybrid nanoparticles about 90 nm in diameter were obtained in both cases, yet Electron Paramagnetic Resonance (EPR) spectroscopy highlighted the different supramolecular organization of HA. The altered HA conformation was reflected in different antioxidant properties of the conjugated nanoparticles that, however, resulted in being higher than for pure HA. Our findings proved the key role of both components in defining the morphology of the final system, as well as the efficacy of the ceramic component in templating the HA supramolecular organization and consequently tuning their functional features, thus defining a green strategy for bio-waste valorization.

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery

In order to evaluate the potential of a technology platform based on hyaluronan copolymers grafted with propargylated ferulate fluorophores (HA-FA-Pg) in the development of drug delivery systems, the propargyl groups of HA-FA-Pg derivatives were employed with oleic acid (OA) or stearic acid (SA) residues across a biocompatible hexa(ethylene glycol) (HEG) spacer. The designed materials (i.e., HA-FA-HEG-OA or HA-FA-HEG-SA) showed clear-cut aggregation features in an aqueous environment, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), generating nanoaggregate systems. In fact, HA-FA-HEG-OA and HA-FA-HEG-SA derivatives showed the property to create self-assembled cytocompatible nanostructured aggregates in water, thanks to the simultaneous presence of hydrophilic portions in the polymeric backbone, such as hyaluronic acid, and hydrophobic portions in the side chains. Furthermore, the designed materials interact with living cells showing a high degree of cytocompatibility. The potential ability of nanosystems to load pharmacologically active molecules was assessed by the physical entrapment of olanzapine into both polymeric systems. The drug loading evaluation demonstrated that the nanoparticles are able to incorporate a good quantity of olanzapine, as well as improve drug solubility, release profile, and cytocompatibility.

Microfluidic Paper-Based Analytical Devices for Colorimetric Detection of Lactoferrin

Lactoferrin is an abundant glycoprotein in human body fluids and is known as a biomarker for various diseases. Therefore, point-of-care testing (POCT) for lactoferrin is of interest. Microfluidic paper-based analytical devices (µPADs) have gained a lot of attention as next-generation POCT device candidates, due to their inexpensiveness, operational simplicity, and being safely disposable. This work presents a colorimetric sensing approach for quantitative lactoferrin analysis. The detection mechanism takes advantage of the high affinity of lactoferrin to ferric ions (Fe3+). Lactoferrin is able to displace an indicator from a colorimetric 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP)-Fe3+ complex, resulting in a color change. A 5-Br-PADAP-Fe3+ complex was encapsulated into water-dispersible poly(styrene- block-vinylpyrrolidone) particles, whose physical entrapment in the cellulosic fiber network results in the immobilization of the complex to the paper matrix. The complex-encapsulating particles showed a color change response in accordance with lactoferrin concentration. Both color intensity-based paper well plates and distance readout-based µPADs are demonstrated. Color intensity-based devices allowed quantitative analysis of lactoferrin concentrations with a limit of detection of 110 µg/mL, using a smartphone and a color readout app. On the other hand, distance readout-based µPADs showed changes of the length of colored sections in accordance with lactoferrin concentration. In summary, we successfully developed both colorimetric intensity-based paper wells and distance-based µPADs for lactoferrin detection. This work demonstrates a user-friendly colorimetric analysis platform for lactoferrin without requiring lab equipment and expensive antibodies.