Evaluating Nanoparticles Penetration by a New Microfluidic Hydrogel-Based Approach.

Reliable predictions for the route and accumulation of nanotherapeutics in vivo are limited by the huge gap between the 2D in vitro assays used for drug screening and the 3D physiological in vivo environment. While developing a standard 3D in vitro model for screening nanotherapeutics remains challenging, multi-cellular tumor spheroids (MCTS) are a promising in vitro model for such screening. Here, we present a straightforward and flexible 3D-model microsystem made out of agarose-based micro-wells, which enables the formation of hundreds of reproducible spheroids in a single pipetting.

Integrated platform for culture, observation, and parallelized electroporation of spheroids.

Reversible electroporation is a method to introduce molecules into cells by increasing the permeability of their membranes, thanks to the application of pulsed electric fields. One of its main biomedical applications is electro-chemotherapy, where electroporation is used to deliver anticancer drugs into tumor tissues. To improve our understanding of the electroporation effect on tissues and select efficient treatments, tumor models are needed.

Correction: Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D platform.

Correction for 'Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D platform' by Saba Goodarzi , , 2021, , 2495-2510, DOI: 10.1039/D1LC00192B.

Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D platform.

The huge gap between 2D in vitro assays used for drug screening and the in vivo 3D physiological environment hampered reliable predictions for the route and accumulation of nanotherapeutics in vivo. For such nanotherapeutics, multi-cellular tumour spheroids (MCTS) are emerging as a good alternative in vitro model. However, the classical approaches to produce MCTS suffer from low yield, slow process, difficulties in MCTS manipulation and compatibility with high-magnification fluorescence optical microscopy.

Mechanical Control of Cell Proliferation Increases Resistance to Chemotherapeutic Agents.

While many cellular mechanisms leading to chemotherapeutic resistance have been identified, there is an increasing realization that tumor-stroma interactions also play an important role. In particular, mechanical alterations are inherent to solid cancer progression and profoundly impact cell physiology. Here, we explore the influence of compressive stress on the efficacy of chemotherapeutics in pancreatic cancer spheroids.

High-Frequency Mechanical Properties of Tumors Measured by Brillouin Light Scattering.

The structure of tumors can be recapitulated as an elastic frame formed by the connected cytoskeletons of the cells invaded by interstitial and intracellular fluids. The low-frequency mechanics of this poroelastic system, dictated by the elastic skeleton only, control tumor growth, penetration of therapeutic agents, and invasiveness. The high-frequency mechanical properties containing the additional contribution of the internal fluids have also been posited to participate in tumor progression and drug resistance, but they remain largely unexplored.

Drug delivery to tumours using a novel 5-FU derivative encapsulated into lipid nanocapsules.

In this work, a novel lipophilic 5-fluorouracil (5-FU) derivative was synthesised and encapsulated into lipid nanocapsules (LNC). 5-FU was modified with lauric acid to give a lipophilic mono-lauroyl-derivative (5-FU-C12, MW of about 342 g/mol, yield of reaction 70%). 5-FU-C12 obtained was efficiently encapsulated into LNC (encapsulation efficiency above 90%) without altering the physico-chemical characteristics of LNC.

Collective regulation of cell motility using an accurate density-sensing system.

The capacity of living cells to sense their population density and to migrate accordingly is essential for the regulation of many physiological processes. However, the mechanisms used to achieve such functions are poorly known. Here, based on the analysis of multiple trajectories of vegetative cells, we investigate such a system extensively.

In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil.

MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-up of MCTS with simple and robust readouts to evaluate drug efficacy is still missing. Here, we evaluate the chemotherapeutic drug 5-Fluorouracil (5-FU) response on the growth and integrity of MCTS two days after treatment of MCTS and for three colorectal carcinoma cell lines with different cohesive properties (HT29, HCT116 and SW480).

Magnetophoretic manipulation in microsystem using carbonyl iron-polydimethylsiloxane microstructures.

This paper reports the use of a recent composite material, noted hereafter i-PDMS, made of carbonyl iron microparticles mixed in a PolyDiMethylSiloxane (PDMS) matrix, for magnetophoretic functions such as capture and separation of magnetic species. We demonstrated that this composite which combine the advantages of both components, can locally generate high gradients of magnetic field when placed between two permanent magnets. After evaluating the magnetic susceptibility of the material as a function of the doping ratio, we investigated the molding resolution offered by i-PDMS to obtain microstructures of various sizes and shapes.

A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stress-dependent motion.

We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment.

A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis.

Background: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase.

The MRI assessment of intraurethrally--delivered muscle precursor cells using anionic magnetic nanoparticles.

Autografting of cultured myogenic precursor cells (MPC) is a therapeutic strategy for muscle disorders, including striated urethral sphincter insufficiency. Implantation of myofibers with their satellite cells into the urethra is a recently described method of MPC transfer aimed at generating a new sphincter in incontinent patients. In this study, we magnetically labeled muscle implants with dextran-free anionic iron oxide nanoparticles (AMNP).

Aortic aneurysms in a rat model: in vivo MR imaging of endovascular cell therapy.

Purpose: To prospectively evaluate in rats whether magnetic cell labeling can be used to noninvasively assess the technical success of endovascular cell therapy for abdominal aortic aneurysms (AAAs).

Materials And Methods: The study was approved by an institutional animal care and use committee. Vascular smooth muscle cells (VSMCs) labeled with iron oxide nanoparticles were seeded endovascularly in already formed AAAs.

Magnetic targeting of nanometric magnetic fluid loaded liposomes to specific brain intravascular areas: a dynamic imaging study in mice.

Purpose: To prospectively determine, by using dynamic imaging, whether a magnet placed over a specific area of the mouse brain could target systemically administered rhodamine-labeled magnetic fluid-loaded liposomes (MFLs) to that brain region.

Materials And Methods: Experiments were performed with a French Ministry of Agriculture permit and regional ethics committee authorization. In seven anesthetized C57BL/6 mice, a closed cranial window was implanted above the left parieto-occipital cortex.

Intraurethral transfer of satellite cells by myofiber implants results in the formation of innervated myotubes exerting tonic contractions.

Purpose: We investigated a new method of muscle precursor cell transfer in the urethra for the treatment of urinary incontinence, consisting of implanting myofibers with their satellite cells.

Materials And Methods: In preliminary experiments to test the regenerative capacities of satellite cells histological analysis was performed on days 7 and 30 after the implantation of myofiber cores in the urethra of 6 female pigs. In the main experiments 11 pigs underwent baseline urodynamics, followed by endoscopic destruction of the striated urethral sphincter located around the distal urethra (day 0).

Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging.

Luminescent hybrid nanoparticles with a paramagnetic Gd2O3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging.

Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation.

Purpose: To perform a quantitative analysis of anionic maghemite nanoparticle-labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging.

Materials And Methods: The study was approved by the institutional animal care and use committee at Hôpital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0-14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles.