Cell-Mimic Directional Cargo Transportation in a Visible-Light-Activated Colloidal Motor/Lipid Tube System

Active tether and transportation of cargoes on cytoskeletal highway enabled by molecular motors is key for accurate delivery of vesicles and organelles in the complex intracellular environment. Here, a hybrid system composed of colloidal motors and self-assembled lipid tubes is designed to mimic the subcellular traffic system in living cells. The colloidal motors, composed of gold-coated hematite, display light-activated self-propulsion tunable by the light intensity and the concentration of hydrogen peroxide fuel. Importantly, the motors show light-switchable binding with lipid cargoes and attachment to the lipid tubes, whereby the latter act as the motor highways. Upon assembly, the colloidal motor/lipid tube system demonstrates directional delivery of lipid vesicles, emulating intracellular transportation. The assembly and function of the hybrid system are rationalized by a cooperative action of light-triggered electrophoretic and hydrodynamic effects, supported by finite element analysis. A synthetic analog of the biological protein motor/cytoskeletal filament system is realized for the manipulation and delivery of different matter at the microscale, which is expected to be a promising platform for various applications in materials science, nanotechnology, microfluidics, and synthetic biology.     

Magnetically Powered Immunogenic Macrophage Microrobots for Targeted Multimodal Cancer Therapy (Small 42/2023)

Motile microrobots open a new realm for disease treatment. However, the concerns of possible immune elimination, targeted capability and limited therapeutic avenue of microrobots constrain its practical biomedical applications. Herein, a biogenic macrophage-based microrobot loaded with magnetic nanoparticles and bioengineered bacterial outer membrane vesicles (OMVs), capable of magnetic propulsion, tumor targeting, and multimodal cancer therapy is reported. Such cell robots preserve intrinsic properties of macrophages for tumor suppression and targeting, and bioengineered OMVs for antitumor immune regulation and fused anticancer peptides. Cell robots display efficient magnetic propulsion and directional migration in the confined space. In vivo tests show that cell robots can accumulate at the tumor site upon magnetic manipulation, coupling with tumor tropism of macrophages to greatly improve the efficacy of its multimodal therapy, including tumor inhibition of macrophages, immune stimulation, and antitumor peptides of OMVs. This technology offers an attractive avenue to design intelligent medical microrobots with remote manipulation and multifunctional therapy capabilities for practical precision treatment.     

Gamma-irradiation of individual cholesterol oxidation products

Cholesterol and seven of its oxidation products in aqueous suspensions of multilamellar vesicles or sonicated aqueous suspensions were subjected individually to γ-radiation (10 KGy) at 0–4°C in air, N₂ or N₂O. All compounds underwent some changes under the influence of radiation. β-Epoxide (cholesterol 5β,6β-epoxide) and, to a much lesser extent, α-epoxide (cholesterol 5α,6α-epoxide) were converted in low yield to 6-ketocholestanol (5α-cholestan-3β-ol-6-one). 7β-Hydroxycholesterol (cholest-5-ene-3β,7β-diol) and, to a lesser extent, 7α-hydroxycholesterol (cholest-5-ene-3β,7α-diol) gave low yields of 7-ketocholestanol (5α-cholestan-3β-ol-7-one). The latter compound also was obtained by irradiation of 7-ketocholesterol (cholest-5-ene-3β-ol-7-one). 6-Ketocholestanol and 7-ketocholestanol are potential biomarkers for irradiated meat and poultry.     

Zinc as an essential trace element in the acceleration of matrix vesicles-mediated mineral deposition

BACKGROUND: Zinc (Zn) has a potent stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. PURPOSE: The effect of Zn on the function of matrix vesicles (MVs) remains controversial. The purpose of this study was to investigate the effect of Zn on alkaline phosphatase (ALP) activity of osteoblasts and in the initial biological MVs‐mediated mineral deposition. STUDY DESIGN: Osteoblasts were treated with varying concentrations of Zn dissolved in culture medium. After three, five, and seven days of culture, ALP activity was assayed. For the detection of a low level of calcium concentration in MVs, X‐ray fluorescence (XRF) analyses were applied. The effect of Zn for the transformation of calcium phosphate was analyzed using a scanning electron microscope fitted with an energy dispersive X‐ray microanalysis (EDX) system. RESULTS: The ALP activity of osteoblasts in culture medium supplemented with 1 × 10^?5M of Zn was significantly increased at both five and seven days. XRF data demonstrated higher levels of calcium concentration over time in the Zn‐supplemented group. EDX data showed that mineral deposits beginning on day 3 were transformed from whitlockite to calcium phosphate near hydroxyapatite, and that Zn accelerated this transformation. CONCLUSIONS: The proper concentration of Zn increased the ALP activity of osteoblasts after five and seven days of incubation. The present XRF and EDX data suggest that the increase of mineral deposition with Zn exposure for one to five days might be mediated by the activation of ALP and calcium‐binding proteins. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.     

Vesicle-templating poly (3,4-ethylenedioxythiophene) hollow microspheres with enhanced electrocatalytic activity toward ascorbic acid oxidation

Poly(3,4-ethylenedioxythiophene) (PEDOT) hollow microspheres ranging from 50 to 950?nm are synthesized by chemically oxidative polymerization of 3,4-ethylenedioxythiophene using ammonium persulfate in the aqueous solution of cetyltrimethylammonium bromide (CTAB) and sodium dodecylbenzenesulfate (SDBS). Vesicles formed by CTAB and SDBS serve as templates for the formation of PEDOT hollow microspheres. The obtained PEDOT hollow microspheres were characterized by Fourier transform infrared spectroscopy, elemental analysis, X-ray photoelectron spectroscopy, and conductivity measurement. Compared to PEDOT granular particles, PEDOT hollow microspheres showed a more effective electrocatalytic activity in lowering the ascorbic acid oxidation potential.     

A two-photon fluorescent probe for lipid raft imaging: C-laurdan

The lipid-rafts hypothesis proposes that naturally occurring lipid aggregates exist in the plane of membrane that are involved in signal transduction, protein sorting, and membrane transport. To understand their roles in cell biology, a direct visualization of such domains in living cells is essential. For this purpose, 6-dodecanoyl-2-(dimethylamino)naphthalene (laurdan), a membrane probe that is sensitive to the polarity of the membrane, has often been used. We have synthesized and characterized 6-dodecanoyl-2-[N-methyl-N-(carboxymethyl)amino]naphthalene (C-laurdan), which has the advantages of greater sensitivity to the membrane polarity, a brighter two-photon fluorescence image, and reflecting the cell environment more accurately than laurdan. Lipid rafts can be visualized by two-photon microscopy by using C-laurdan as a probe. Our results show that the lipid rafts cover 38 % of the cell surface.     

One Hundred Million Years of Chemical Warfare by Insects

An important defensive strategy among animals is the use of chemical compounds with toxic or irritating properties. In this paper, we report the discovery of an Early Cretaceous soldier beetle (Coleoptera: Cantharidae) in Burmese amber that seemingly employed a chemical defense response against a potential predator. Six pairs of cuticular vesicles with associated gland reservoirs were extruded from the insect’s abdomen, and a secretion released from one of these covers a portion of the antenna of a second insect species, considered to be the perpetrator of the response. This is the earliest fossil record of a putative chemical defense response and suggests that chemical defense mechanisms in beetles have been in existence for at least 100 Ma.     

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) ({"type":"clinical-trial","attrs":{"text":"NCT02195726","term_id":"NCT02195726"}}NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.