Disorder-Induced Anomalous Mobility Enhancement in Confined Geometries.

Strong, scale-free disorder disrupts typical transport properties like the Stokes-Einstein relation and linear response, leading to anomalous diffusion observed in amorphous materials, glasses, living cells, and other systems. Our study reveals that the combination of scale-free quenched disorder and geometrical constraints induces unconventional single-particle mobility behavior. Specifically, in a two-dimensional channel with width w, under external drive, tighter geometrical constraints (smaller w) enhance mobility.

Universal to nonuniversal transition of the statistics of rare events during the spread of random walks.

Through numerous experiments that analyzed rare event statistics in heterogeneous media, it was discovered that in many cases the probability density function for particle position, P(X,t), exhibits a slower decay rate than the Gaussian function. Typically, the decay behavior is exponential, referred to as Laplace tails. However, many systems exhibit an even slower decay rate, such as power-law, log-normal, or stretched exponential.

Triggering Gaussian-to-Exponential Transition of Displacement Distribution in Polymer Nanocomposites Adsorption-Induced Trapping.

In many disordered systems, the diffusion of classical particles is described by a displacement distribution (, ) that displays exponential tails instead of Gaussian statistics expected for Brownian motion. However, the experimental demonstration of control of this behavior by increasing the disorder strength has remained challenging. In this work, we explore the Gaussian-to-exponential transition by using diffusion of poly(ethylene glycol) (PEG) in attractive nanoparticle-polymer mixtures and controlling the volume fraction of the nanoparticles.

Doxorubicin-Loaded Polyelectrolyte Multilayer Capsules Modified with Antitumor DR5-Specific TRAIL Variant for Targeted Drug Delivery to Tumor Cells.

Recently, biodegradable polyelectrolyte multilayer capsules (PMC) have been proposed for anticancer drug delivery. In many cases, microencapsulation allows to concentrate the substance locally and prolong its flow to the cells. To reduce systemic toxicity when delivering highly toxic drugs, such as doxorubicin (DOX), the development of a combined delivery system is of paramount importance.

Self-assembly of two-dimensional, amorphous materials on a liquid substrate.

Recent experimental utilization of liquid substrate in the production of two-dimensional crystals, such as graphene, together with a general interest in amorphous materials, raises the following question: is it beneficial to use a liquid substrate to optimize amorphous material production? Inspired by epitaxial growth, we use a two-dimensional coarse-grained model of interacting particles to show that introducing a motion for the substrate atoms improves the self-assembly process of particles that move on top of the substrate. We find that a specific amount of substrate liquidity (for a given sample temperature) is needed to achieve optimal self-assembly. Our results illustrate the opportunities that the combination of different degrees of freedom provides to the self-assembly processes.

Cusp of Non-Gaussian Density of Particles for a Diffusing Diffusivity Model.

We study a two state "jumping diffusivity" model for a Brownian process alternating between two different diffusion constants, D+>D-, with random waiting times in both states whose distribution is rather general. In the limit of long measurement times, Gaussian behavior with an effective diffusion coefficient is recovered. We show that, for equilibrium initial conditions and when the limit of the diffusion coefficient D-⟶0 is taken, the short time behavior leads to a cusp, namely a non-analytical behavior, in the distribution of the displacements P(x,t) for x⟶0.

From diffusion in compartmentalized media to non-Gaussian random walks.

In this work we establish a link between two different phenomena that were studied in a large and growing number of biological, composite and soft media: the diffusion in compartmentalized environment and the non-Gaussian diffusion that exhibits linear or power-law growth of the mean square displacement joined by the exponential shape of the positional probability density. We explore a microscopic model that gives rise to transient confinement, similar to the one observed for hop-diffusion on top of a cellular membrane. The compartmentalization of the media is achieved by introducing randomly placed, identical barriers.

Large Deviations for Continuous Time Random Walks.

Recently observation of random walks in complex environments like the cell and other glassy systems revealed that the spreading of particles, at its tails, follows a spatial exponential decay instead of the canonical Gaussian. We use the widely applicable continuous time random walk model and obtain the large deviation description of the propagator. Under mild conditions that the microscopic jump lengths distribution is decaying exponentially or faster i.

Fabrication and evaluation of nanocontainers for lipophilic anticancer drug delivery in 3D in vitro model.

Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed.

Novel bexarotene derivatives: Synthesis and cytotoxicity evaluation for glioma cells in 2D and 3D in vitro models.

Glioblastoma (GBM) is an aggressive and lethal form of brain cancer with a high invasion capacity and a lack of effective chemotherapeutics. Retinoid bexarotene (BXR) inhibits the neurospheroidal colony formation and migration of primary glioblastoma cells but has side effects. To enhance the BXR glioblastoma selectivity and cytotoxicity, we chemically modified it at the carboxyl group with either nitroethanolamine (NEA) bearing a NO-donating group (a well-known bioactivity enhancer; BXR-NEA) or with a dopamine (DA) moiety (to represent the highly toxic for various tumor cells N-acyldopamine family; BXR-DA).

A Triple Combination of Metformin, Acetylsalicylic Acid, and Oseltamivir Phosphate Impacts Tumour Spheroid Viability and Upends Chemoresistance in Triple-Negative Breast Cancer.

Introduction: Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen.

Impact of Fucosylation on Self-Assembly of Prostate and Breast Tumor Spheroids by Using Cyclo-RGDfK(TPP) Peptide and Image Object Detection.

Introduction: Core fucosylation of N-glycans on the integrin β1 subunit is essential for the functional activity of the integrin. The binding of α5β1 integrin with the tripeptide Arg-Gly-Asp (RGD) motif within the extracellular matrix protein fibronectin may be influenced by the α-1,6-fucose core or α-1,2-fucose and α-1,3/4-fucose peripheral N-glycan profiles. Here, we investigated whether fucosylation impacts the formation of matrix-free 3D multicellular tumor spheroids (MCTS) from human triple negative breast MDA-MB231 cell line, prostate PC3 and DU145 cell lines and DU145 gemcitabine resistant (GemR) variant by using the cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP)) peptide method.

The effect of disordered substrate on crystallization in 2D.

In this work, the effect of amorphous substrate on crystallization is addressed. By performing Monte-Carlo simulations of solid on solid models, we explore the effect of the disorder on crystal growth. The disorder is introduced via local geometry of the lattice, where local connectivity and transition rates are varied from site to site.

Lipoamino acid-based cerasomes for doxorubicin delivery: Preparation and in vitro evaluation.

Cerasomes are hybrid organic-inorganic nanoparticles (NPs) that could be considered as liposomes with rather durable silicon shell. In this study, several cerasome-forming lipoamino acids (CFLA) were synthesized and used as structural blocks for cerasome preparation. Pure cerasomes which contained only CFLA, and mixed cerasomes based on a mixture of CFLA with a disintegrating dipalmitoylphosphatidylcholine (DPPC) lipid were fabricated and characterized in terms of morphology, mean size, ζ-potential, stability at storage.

Metformin increases antitumor activity of MEK inhibitor binimetinib in 2D and 3D models of human metastatic melanoma cells.

Melanoma is one of the most aggressive and treatment-resistant tumors that responsible for majority of skin-cancer related deaths. Here we propose a combination of MEK inhibitor binimetinib with metformin as a promising therapy against human melanoma cells in vitro, including BRAF -mutated A375, Mel Z, and Mel IL cells, and NRAS-mutated Mel MTP and Mel Me cells. Additionally, we obtained two close to clinical practice models of melanoma progression.

Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core.

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a "smart" drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge.

Novel Doxorubicin Derivatives: Synthesis and Cytotoxicity Study in 2D and 3D Models.

Multidrug resistance (MDR) of tumors to chemotherapeutics often leads to failure of cancer treatment. The aim of the study was to prepare novel MDR-overcoming chemotherapeutics based on doxorubicin (DOX) derivatives and to evaluate their efficacy in 2D and 3D in vitro models. To overcome MDR, we synthesized five DOX derivatives, and then obtained non-covalent complexes with human serum albumin (HSA).

From quenched disorder to continuous time random walk.

This work focuses on quantitative representation of transport in systems with quenched disorder. Explicit mapping of the quenched trap model to continuous time random walk is presented. Linear temporal transformation, t→t/Λ^{1/α}, for a transient process in the subdiffusive regime is sufficient for asymptotic mapping.

Stochastic maps, continuous approximation, and stable distribution.

A continuous approximation framework for general nonlinear stochastic as well as deterministic discrete maps is developed. For the stochastic map with uncorelated Gaussian noise, by successively applying the Itô lemma, we obtain a Langevin type of equation. Specifically, we show how nonlinear maps give rise to a Langevin description that involves multiplicative noise.

Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using cyclo-RGDfK(TPP) peptide.

Background: Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell-cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking in vivo tumors, the limitations involve no control of assembly and structure with only limited spatial or glandular organization. Here, matrix-free prostaspheres from human metastatic prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP)).

Driven optical matter: Dynamics of electrodynamically coupled nanoparticles in an optical ring vortex.

To date investigations of the dynamics of driven colloidal systems have focused on hydrodynamic interactions and often employ optical (laser) tweezers for manipulation. However, the optical fields that provide confinement and drive also result in electrodynamic interactions that are generally neglected. We address this issue with a detailed study of interparticle dynamics in an optical ring vortex trap using 150-nm diameter Ag nanoparticles.

Single-pixel interior filling function approach for detecting and correcting errors in particle tracking.

We present a general method for detecting and correcting biases in the outputs of particle-tracking experiments. Our approach is based on the histogram of estimated positions within pixels, which we term the single-pixel interior filling function (SPIFF). We use the deviation of the SPIFF from a uniform distribution to test the veracity of tracking analyses from different algorithms.

Noisy oscillator: Random mass and random damping.

The problem of a linear damped noisy oscillator is treated in the presence of two multiplicative sources of noise which imply a random mass and random damping. The additive noise and the noise in the damping are responsible for an influx of energy to the oscillator and its dissipation to the surrounding environment. A random mass implies that the surrounding molecules not only collide with the oscillator but may also adhere to it, thereby changing its mass.

Oxime ligation in acetic acid: efficient synthesis of aminooxy-peptide conjugates.

Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reaction rates and quantitative yields are typically reported for aldehyde-derived compounds. In contrary, keto groups react much slower, with quantitative yields achieved at 5 h for low-molecular weight compounds and more than 15 h for polymers or dendrimers.