Optical Methods for Determining the Phagocytic Activity Profile of CD206-Positive Macrophages Extracted from Bronchoalveolar Lavage by Specific Mannosylated Polymeric Ligands.

Macrophage (Mph) polarization and functional activity play an important role in the development of inflammatory lung conditions. The previously widely used bimodal classification of Mph into M1 and M2 does not adequately reflect the full range of changes in polarization and functional diversity observed in Mph in response to various stimuli and disease states. Here, we have developed a model for the direct assessment of Mph from bronchial alveolar lavage fluid (BALF) functional alterations, in terms of phagocytosis activity, depending on external stimuli, such as exposure to a range of bacteria (, and ).

Polymeric Infrared and Fluorescent Probes to Assess Macrophage Diversity in Bronchoalveolar Lavage Fluid of Asthma and Other Pulmonary Disease Patients.

Bronchial asthma remains a serious medical problem, as approximately 10% of patients fail to achieve adequate symptom control with available treatment options. Macrophages play a pivotal role in the pathophysiology of asthma, as well as in some other respiratory disorders. Typically, they are classified into two major classes, M1 and M2; however, recent findings have indicated that in fact there is a whole range of macrophage polarization and functional diversity beyond this bimodal division.

Classical View on Nonclassical Crystal Growth in a Biological Setting.

Crystallization by amorphous particle attachment, a nonclassical crystal growth mode, is prevalent in minerals formed by living tissues. It allows the organism to intervene at every step of crystal growth, i.e.

Bacterial Cellulose-Chitosan Composite for Prolonged-Action L-Asparaginase in Treatment of Melanoma Cells.

A significant challenge associated with the therapeutic use of L-ASP for treatment of tumors is its rapid clearance from plasma. Effectiveness of L-ASP is limited by the dose-dependent toxicity. Therefore, new approaches are being developed for L-ASP to improve its therapeutic properties.

pH-Sensitive Fluorescent Probe in Nanogel Particles as Theragnostic Agent for Imaging and Elimination of Latent Bacterial Cells Residing Inside Macrophages.

Rhodamine 6G (R6G) and 4-nitro-2,1,3-benzoxadiazole (NBD) linked through a spacer molecule spermidine (spd), R6G-spd-NBD, produces a fluorescent probe with pH-sensitive FRET (Förster (fluorescence) resonance energy transfer) effect that can be useful in a variety of diagnostic applications. Specifically, cancer cells can be spotted due to a local decrease in pH (Warburg effect). In this research, we applied this approach to intracellular infectious diseases-namely, leishmaniasis, brucellosis, and tuberculosis, difficult to treat because of their localization inside macrophages.

pH-Sensitive Fluorescent Marker Based on Rhodamine 6G Conjugate with Its FRET/PeT Pair in "Smart" Polymeric Micelles for Selective Imaging of Cancer Cells.

Cancer cells are known to create an acidic microenvironment (the Warburg effect). At the same time, fluorescent dyes can be sensitive to pH, showing a sharp increase or decrease in fluorescence depending on pH. However, modern applications, such as confocal laser scanning microscopy (CLSM), set additional requirements for such fluorescent markers to be of practical use, namely, high quantum yield, low bleaching, minimal quenching in the cell environment, and minimal overlap with auto-fluorophores.

Targeted Polymeric Micelles System, Designed to Carry a Combined Cargo of L-Asparaginase and Doxorubicin, Shows Vast Improvement in Cytotoxic Efficacy.

L-asparaginases (ASP) and Doxorubicin (Dox) are both used in the treatment of leukemia, including in combination. We have attempted to investigate if their combination within the same targeted delivery vehicle can make such therapy more efficacious. We assembled a micellar system, where the inner hydrophobic core was loaded with Dox, while ASP would absorb at the surface due to electrostatic interactions.

Elastic constants of biogenic calcium carbonate.

Living organisms form complex mineralized composite architectures that perform a variety of essential functions. These materials are commonly utilized for load-bearing purposes such as structural stability and mechanical strength in combination with high toughness and deformability, which are well demonstrated in various highly mineralized molluscan shell ultrastructures. Here, the mineral components provide the general stiffness to the composites, and the organic interfaces play a key role in providing these biogenic architectures with mechanical superiority.

Disulfide Cross-Linked Polymeric Redox-Responsive Nanocarrier Based on Heparin, Chitosan and Lipoic Acid Improved Drug Accumulation, Increased Cytotoxicity and Selectivity to Leukemia Cells by Tumor Targeting via "Aikido" Principle.

We have developed a micellar formulation of anticancer drugs based on chitosan and heparin grafted with lipoic and oleic acids that can release the cytotoxic cargo (doxorubicin) in response to external stimuli, such as increased glutathione concentration-a hallmark of cancer. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of the nanocarrier: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (tumor microenvironment). Fatty acid residues are necessary for the formation of nanoparticles (micelles) and solubilization of cytostatics in a hydrophobic core.

Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations.

Allylbenzenes (apiol, dillapiol, myristicin and allyltetramethoxybenzene) are individual components of plant essential oils that demonstrate antitumor activity and can enhance the antitumor activity of cytotoxic drugs, such as paclitaxel, doxorubicin, cisplatin, etc. Triphenylphosphine (PPh) derivatives of allylbenzenes are two to three orders of magnitude more potent than original allylbenzenes in terms of IC. The inhibition of efflux pumps has been reported for allylbenzenes, and the PPh moiety is deemed to be responsible for preferential mitochondrial accumulation and the depolarization of mitochondrial membranes.

Biomimetic Systems Involving Macrophages and Their Potential for Targeted Drug Delivery.

The concept of targeted drug delivery can be described in terms of the drug systems' ability to mimic the biological objects' property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently.

Biomimetic System Based on Reconstituted Macrophage Membranes for Analyzing and Selection of Higher-Affinity Ligands Specific to Mannose Receptor to Develop the Macrophage-Focused Medicines.

Progress in macrophage research is crucial for numerous applications in medicine, including cancer and infectious diseases. However, the existing methods to manipulate living macrophages are labor-intense and inconvenient. Here, we show that macrophage membranes can be reconstituted after storage for months at 4 °C, with their CD206 receptor selectivity and specificity being similar to those in the living cells.

Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract.

Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited.

Physical Phenomena Governing Mineral Morphogenesis in Molluscan Nacre.

Mollusks, as well as many other living organisms, have the ability to shape mineral crystals into unconventional morphologies and to assemble them into complex functional mineral-organic structures, an observation that inspired tremendous research efforts in scientific and technological domains. Despite these, a biochemical toolkit that accounts for the formation of the vast variety of the observed mineral morphologies cannot be identified yet. Herein, phase-field modeling of molluscan nacre formation, an intensively studied biomineralization process, is used to identify key physical parameters that govern mineral morphogenesis.

Nanoscale dynamic mechanical analysis on interfaces of biological composites.

Biological composites incorporate structural arrays of rigid-elastic reinforcements made of minerals or crystalline biopolymers, which are connected by thin, compliant, and viscoelastic macromolecular matrix material. The near-interface regions of these biological composites grant them energy dissipation capabilities against dynamic mechanical loadings, which promote various biomechanical functions such as impact adsorption, fracture toughness, and mechanical signal filtering. Here, we employ theoretical modeling and finite-element simulations to analyze the mechanical response of the near-interface in biological composites to nanoscale dynamic mechanical analysis (DMA).

Covalent Conjugates of Allylbenzenes and Terpenoids as Antibiotics Enhancers with the Function of Prolonged Action.

The drug resistance of pathogenic bacteria is often due efflux pumps-specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the action of antibiotics. We assumed that a new level of effectiveness with the use of an antibiotic + an adjuvant pair could be achieved by their joint delivery into the pathogen.

Fluorescent Probes with Förster Resonance Energy Transfer Function for Monitoring the Gelation and Formation of Nanoparticles Based on Chitosan Copolymers.

Nanogel-forming polymers such as chitosan and alginic acid have a number of practical applications in the fields of drug delivery, food technology and agrotechnology as biocompatible, biodegradable polymers. Unlike bulk macrogel formation, which is followed by visually or easily detectable changes and physical parameters, such as viscosity or turbidity, the formation of nanogels is not followed by such changes and is therefore very difficult to track. The counterflow extrusion method (or analogues) enables gel nanoparticle formation for certain polymers, including chitosan and its derivatives.

Fractal-like geometry as an evolutionary response to predation?

Fractal-like, intricate morphologies are known to exhibit beneficial mechanical behavior in various engineering and technological domains. The evolution of fractal-like, internal walls of ammonoid cephalopod shells represent one of the most clear evolutionary trends toward complexity in biology, but the driver behind their iterative evolution has remained unanswered since the first hypotheses introduced in the early 1800s. We show a clear correlation between the fractal-like morphology and structural stability.

Polymeric Micelles Formulation of Combretastatin Derivatives with Enhanced Solubility, Cytostatic Activity and Selectivity against Cancer Cells.

Combretastatin derivatives is a promising class of antitumor agents, tubulin assembly inhibitors. However, due to poor solubility and insufficient selectivity to tumor cells, we believe, their therapeutic potential has not been fully realized yet. This paper describes polymeric micelles based on chitosan (a polycation that causes pH and thermosensitivity of micelles) and fatty acids (stearic, lipoic, oleic and mercaptoundecanoic), which were used as a carrier for a range of combretastatin derivatives and reference organic compounds, demonstrating otherwise impossible delivery to tumor cells, at the same time substantially reduced penetration into normal cells.

Thermoreversible Gels Based on Chitosan Copolymers as "Intelligent" Drug Delivery System with Prolonged Action for Intramuscular Injection.

Thermosensitive gels based on copolymers (PEG-chitosan, chitosan-polyethylenimine, chitosan-arginine and glycol-chitosan-spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic.

Smart pH- and Temperature-Sensitive Micelles Based on Chitosan Grafted with Fatty Acids to Increase the Efficiency and Selectivity of Doxorubicin and Its Adjuvant Regarding the Tumor Cells.

The main factors that determine the low effectiveness of chemotherapy are the low target bioavailability of antitumor drugs and the efflux process. In attempts to overcome this problem, several approaches are proposed here. Firstly, the development of polymeric micellar systems based on chitosan grafted by fatty acids (different types to optimize their properties), which, on the one hand, increase the solubility and bioavailability of cytostatics and, on the other hand, effectively interact with tumor cells due to the polycationic properties of chitosan, allowing for more effective penetration of cytostatic drugs into the cells.