All Roads Lead to Rome: Comparing Nanoparticle- and Small Molecule-Driven Cell Autophagy.

Autophagy, vital for removing cellular waste, is triggered differently by small molecules and nanoparticles. Small molecules, like rapamycin, non-selectively activate autophagy by inhibiting the mTOR pathway, which is essential for cell regulation. This can clear damaged components but may cause cytotoxicity with prolonged use. Nanoparticles, however, induce autophagy, often causing oxidative stress, through broader cellular interactions and can lead to a targeted form known as "xenophagy." Their impact varies with their properties but can be harnessed therapeutically. In this review, the autophagy induced by nanoparticles is explored and small molecules across four dimensions: the mechanisms behind autophagy induction, the outcomes of such induction, the toxicological effects on cellular autophagy, and the therapeutic potential of employing autophagy triggered by nanoparticles or small molecules. Although small molecules and nanoparticles each induce autophagy through different pathways and lead to diverse effects, both represent invaluable tools in cell biology, nanomedicine, and drug discovery, offering unique insights and therapeutic opportunities.

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research.

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs) as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing, and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques (microscopy procedures that do not require sample staining) that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focuses on the synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HTM) strategy. HTM is a technique that combines holography and tomography using a low intensity continuous illumination laser to investigate (quantitatively and non-invasively) cells, microorganisms, and thin tissue by generating three-dimensional (3D) images and monitoring in real-time inner morphological changes. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HTM and AFM, which are essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of NMs with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HTM enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including the morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HTM is ideal for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology (study of the harmful effects of NMs in living organisms), emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line.

Bare and doped zinc oxide nanomaterials (ZnO NMs) are of great interest as multifunctional platforms for biomedical applications. In this study, we systematically investigate the physicochemical properties of Aluminum doped ZnO (AZO) and its bio-interactions with neuroblastoma (SH-SY5Y) and red blood (RBCs) cells. We provide a comprehensive chemical and structural characterization of the NMs. We also evaluated the biocompatibility of AZO NMs using traditional toxicity assays and advanced microscopy techniques. The toxicity of AZO NMs towards SH-SY5Y cells, decreases as a function of Al doping but is higher than the toxicity of ZnO NMs. Our results show that N-acetyl cysteine protects SH-SY5Y cells against reactive oxygen species toxicity induced by AZO NMs. ZnO and AZO NMs do not exert hemolysis in human RBCs at the doses that cause toxicity (IC50) in neuroblastoma cells. The Atomic force microscopy qualitative analysis of the interaction of SH-SY5Y cells with AZO NMs shows evidence that the affinity of the materials with the cells results in morphology changes and diminished interactions between neighboring cells. The holotomographic microscopy analysis demonstrates NMs' internalization in SH-SY5Y cells, changes in their chemical composition, and the role of lipid droplets in the clearance of toxicants.

Biocompatibility Evaluation of TiO2, Fe3O4, and TiO2/Fe3O4 Nanomaterials: Insights into Potential Toxic Effects in Erythrocytes and HepG2 Cells.

Nanomaterials such as titanium dioxide and magnetite are increasingly used in several fields, such as water remediation and agriculture. However, this has raised environmental concerns due to potential exposure to organisms like humans. Nanomaterials can cause adverse interactions depending on physicochemical characteristics, like size, morphology, and composition, when interacting with living beings. To ensure safe use and prevent the risk of exposure to nanomaterials, their biocompatibility must be assessed. In vitro cell cultures are beneficial for assessing nanomaterial-cell interactions due to their easy handling. The present study evaluated the biocompatibility of TiO2, Fe3O4, and TiO2/Fe3O4 nanomaterials thermally treated at 350 °C and 450 °C in erythrocytes and HepG2 cells. According to the hemolysis experiments, non-thermally treated NMs are toxic (>5% hemolysis), but their thermally treated counterparts do not present toxicity (<2%). This behavior indicates that the toxicity derives from some precursor (solvent or surfactant) used in the synthesis of the nanomaterials. All the thermally treated nanomaterials did not show hemolytic activity under different conditions, such as low-light exposure or the absence of blood plasma proteins. In contrast, non-thermally treated nanomaterials showed a high hemolytic behavior, which was reduced after the purification (washing and thermal treatment) of nanomaterials, indicating the presence of surfactant residue used during synthesis. An MTS cell viability assay shows that calcined nanomaterials do not reduce cell viability (>11%) during 24 h of exposure. On the other hand, a lactate dehydrogenase leakage assay resulted in a higher variability, indicating that several nanomaterials did not cause an increase in cell death as compared to the control. However, a holotomographic microscopy analysis reveals a high accumulation of nanomaterials in the cell structure at a low concentration (10 µg mL-1), altering cell morphology, which could lead to cell membrane damage and cell viability reduction.

Synthesis of TiO2-Cu2+/CuI Nanocomposites and Evaluation of Antifungal and Cytotoxic Activity.

Fungal infections have become a significant public health concern due to their increasing recurrence and harmful effects on plants, animals, and humans. Opportunistic pathogens (among others from the genera Candida and Aspergillus) can be present in indoor air, becoming a risk for people with suppressed immune systems. Engineered nanomaterials are novel alternatives to traditional antifungal therapy. In this work, copper(I) iodide (CuI) and a copper-doped titanium dioxide-copper(I) iodide (TiO2-Cu2+/CuI) composite nanomaterials (NMs)-were synthesized and tested as antifungal agents. The materials were synthesized using sol-gel (TiO2-Cu2+) and co-precipitation (CuI) techniques. The resulting colloids were evaluated as antifungal agents against Candida parapsilosis and Aspergillus niger strains. The NMs were characterized by XRD, HRTEM, AFM, and DLS to evaluate their physicochemical properties. The NMs present a high size dispersion and different geometrical shapes of agglomerates. The antifungal capacity of the NMs by the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) was below 15 µg/mL against Candida parapsilosis and below 600 µg/mL against Aspergillus niger for both NMs. Holotomography microscopy showed that the NMs could penetrate cell membranes causing cell death through its rupture and reactive oxygen species (ROS) production. Cytotoxicity tests showed that NMs could be safe to use at low concentrations. The synthesized nanomaterials could be potential antifungal agents for biomedical or environmental applications.

A multiconsistent computational methodology to resolve a diffusive epidemiological system with effects of migration, vaccination and quarantine.

BACKGROUND: We provide a compartmental model for the transmission of some contagious illnesses in a population. The model is based on partial differential equations, and takes into account seven sub-populations which are, concretely, susceptible, exposed, infected (asymptomatic or symptomatic), quarantined, recovered and vaccinated individuals along with migration. The goal is to propose and analyze an efficient computer method which resembles the dynamical properties of the epidemiological model. MATERIALS AND METHODS: A non-local approach is utilized for finding approximate solutions for the mathematical model. To that end, a non-standard finite-difference technique is introduced. The finite-difference scheme is a linearly implicit model which may be rewritten using a suitable matrix. Under suitable circumstances, the matrices representing the methodology are M-matrices. RESULTS: Analytically, the local asymptotic stability of the constant solutions is investigated and the next generation matrix technique is employed to calculate the reproduction number. Computationally, the dynamical consistency of the method and the numerical efficiency are investigated rigorously. The method is thoroughly examined for its convergence, stability, and consistency. CONCLUSIONS: The theoretical analysis of the method shows that it is able to maintain the positivity of its solutions and identify equilibria. The method's local asymptotic stability properties are similar to those of the continuous system. The analysis concludes that the numerical model is convergent, stable and consistent, with linear order of convergence in the temporal domain and quadratic order of convergence in the spatial variables. A computer implementation is used to confirm the mathematical properties, and it confirms the ability in our scheme to preserve positivity, and identify equilibrium solutions and their local asymptotic stability.

An efficient nonstandard computer method to solve a compartmental epidemiological model for COVID-19 with vaccination and population migration.

BACKGROUND AND OBJECTIVE: In this manuscript, we consider a compartmental model to describe the dynamics of propagation of an infectious disease in a human population. The population considers the presence of susceptible, exposed, asymptomatic and symptomatic infected, quarantined, recovered and vaccinated individuals. In turn, the mathematical model considers various mechanisms of interaction between the sub-populations in addition to population migration. METHODS: The steady-state solutions for the disease-free and endemic scenarios are calculated, and the local stability of the equilibium solutions is determined using linear analysis, Descartes' rule of signs and the Routh-Hurwitz criterion. We demonstrate rigorously the existence and uniqueness of non-negative solutions for the mathematical model, and we prove that the system has no periodic solutions using Dulac's criterion. To solve this system, a nonstandard finite-difference method is proposed. RESULTS: As the main results, we show that the computer method presented in this work is uniquely solvable, and that it preserves the non-negativity of initial approximations. Moreover, the steady-state solutions of the continuous model are also constant solutions of the numerical scheme, and the stability properties of those solutions are likewise preserved in the discrete scenario. Furthermore, we establish the consistency of the scheme and, using a discrete form of Gronwall's inequality, we prove theoretically the stability and the convergence properties of the scheme. For convenience, a Matlab program of our method is provided in the appendix. CONCLUSIONS: The computer method presented in this work is a nonstandard scheme with multiple dynamical and numerical properties. Most of those properties are thoroughly confirmed using computer simulations. Its easy implementation make this numerical approach a useful tool in the investigation on the propagation of infectious diseases. From the theoretical point of view, the present work is one of the few papers in which a nonstandard scheme is fully and rigorously analyzed not only for the dynamical properties, but also for consistently, stability and convergence.

Development of Nano-Antifungal Therapy for Systemic and Endemic Mycoses.

Fungal mycoses have become an important health and environmental concern due to the numerous deleterious side effects on the well-being of plants and humans. Antifungal therapy is limited, expensive, and unspecific (causes toxic effects), thus, more efficient alternatives need to be developed. In this work, Copper (I) Iodide (CuI) nanomaterials (NMs) were synthesized and fully characterized, aiming to develop efficient antifungal agents. The bioactivity of CuI NMs was evaluated using Sporothrix schenckii and Candida albicans as model organisms. CuI NMs were prepared as powders and as colloidal suspensions by a two-step reaction: first, the CuI2 controlled precipitation, followed by hydrazine reduction. Biopolymers (Arabic gum and chitosan) were used as surfactants to control the size of the CuI materials and to enhance its antifungal activity. The materials (powders and colloids) were characterized by SEM-EDX and AFM. The materials exhibit a hierarchical 3D shell morphology composed of ordered nanostructures. Excellent antifungal activity is shown by the NMs against pathogenic fungal strains, due to the simultaneous and multiple mechanisms of the composites to combat fungi. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of CuI-AG and CuI-Chitosan are below 50 µg/mL (with 5 h of exposition). Optical and Atomic Force Microscopy (AFM) analyses demonstrate the capability of the materials to disrupt biofilm formation. AFM also demonstrates the ability of the materials to adhere and penetrate fungal cells, followed by their lysis and death. Following the concept of safe by design, the biocompatibility of the materials was tested. The hemolytic activity of the materials was evaluated using red blood cells. Our results indicate that the materials show an excellent antifungal activity at lower doses of hemolytic disruption.

Self-cleaning of SiO2-TiO2 coating: Effect of sonochemical synthetic parameters on the morphological, mechanical, and photocatalytic properties of the films.

Among the different properties of the hydrophobic semiconductor surfaces, self-cleaning promoted by solar illumination is probably one of the most attractive from the technological point of view. The use of sonochemistry for nanomaterials' synthesis has been recently employed for the associated shorter reaction times and efficient route for control over crystal growth and the management of the resulting material's photocatalytic properties. Moreover, the sol-gel method coupled to sonochemistry modifies the chemical environment, with reactive species such as •OH and H2O2, which yield a homogeneous synthesis. Therefore, in the following investigation, the sol-gel method was coupled to sonochemistry to synthesize a SiO2@TiO2 composite, for which the sonochemical amplitude of irradiation was varied to determine its effect on the morphology and mechanical and self-cleaning properties. SEM and AFM characterized the samples of SiO2@TiO2 composite, and while the micrographs indicate that a high ultrasonic energy results in an amorphous SiO2@TiO2 composite with a low rugosity, which was affected in the determination of the contact angle on the surface. On the other hand, FTIR analysis suggests a significant change in both SiO2-SiO and SiO2-TiO2 chemical bonds with changes in vibrations and frequency, corroborating an important influence of the sonochemical energy contribution to the hydrolysis process. Raman spectroscopy confirms the presence of an amorphous phase of silicon dioxide; however, the vibrations of TiO2 were not visible. The evaluation of hydrophobic and self-cleaning properties shows a maximum of ultrasonic energy needed to improve the contact angle and rhodamine B (RhB) removal.

Evaluation of the environmental impact of magnetic nanostructured materials at different trophic levels.

Safety on the use of magnetic nanomaterials (MNMs) has become an active topic of research given all the recent applications of these materials in various fields. It is known that the toxicity of MNMs depends on size, shape, and surface functionalization. In this study, we evaluate the biocompatibility with different aquatic organisms of engineered MNMs-CIT with excellent aqueous dispersion and long-term colloidal stability. Primary producers (the alga Pseudokirchneriella subcapitata), primary consumers (the rotifer Lecane papuana), and predators (the fish, Danio rerio) interacted with these materials in acute and sub-chronic toxicity tests. Our results indicate that P. subcaptita was the most sensitive taxon to MNMs-CIT. Inhibition of their population growth (IC50 = 22.84 mg L-1) elicited cell malformations and increased the content of photosynthetic pigments, likely due to inhibition of cell division (as demonstrated in AFM analysis). For L. papuana, the acute exposure to MNMs shows no significant mortality. However, adverse effects such as decreased rate of population and altered swimming patterns arise after chronic interaction with MNMs. For D. rerio organisms on early life stages, their exposure to MNMs results in delayed hatching of eggs, diminished survival of larvae, altered energy resources allocation (measured as the content of total carbohydrates, lipids, and protein), and increased glucose demand. As to our knowledge, this is the first study that includes three different trophic levels to assess the effect of MNMs in aquatic organisms; furthermore, we demonstrated that these MNMs pose hazards on aquatic food webs at low concentrations (few mgL-1).

Development of a sustainable photocatalytic process for air purification.

Nowadays, air pollution has become a global menace being responsible of a significant increase on the morbidity and mortality of human beings. In view of this, sustainable and efficient technologies for air purification are being sought. Air purification by photocatalytic treatment has received a lot of attention due to the unspecific and high oxidation capacity of the catalyst; however still some variables must be optimized to assure practical applications. In this work, visible light active TiO2-Cu2+@perlite and Ag@TiO2-Cu2+/perlite supported materials were fabricated. TiO2-Cu2+ (2 at. %) were synthesized using a sol-gel procedure followed of the impregnation of the support by immersion. For Ag@TiO2-Cu2+, silver deposition was conducted by chemical reduction using sodium citrate and sodium borohydride. The materials (powders and supported materials) were characterized by Scanning Electron Microscopy (SEM) to demonstrate their small size and adherence to the substrate. A prototype of a photocatalytic air purifier was built. The efficacy of the prototype was evaluated for the disinfection of indoor air (dentistry clinics). The photo-catalyst was activated using visible and UVA low-cost high-energy LEDs. The antibacterial activity of the air filter was evaluated. Ag@TiO2-Cu2+ exerts better air disinfection activity at lower doses in comparison to TiO2-Cu2+. Bacterial growth inhibitions up to 99% were achieved for both, Gram-negative and Gram-positive bacteria. The incorporation of Ag and Cu to TiO2 improves the antibacterial activity of the materials due to enhanced photocatalytic activity and the synergic activity of TiO2 and dopant elements (Ag, Cu) to inhibit microorganism's growth.

Development and Assessment of Nano-Technologies for Cancer Treatment: Cytotoxicity and Hyperthermia Laboratory Studies.

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.

Tetrakis(mu-triisopropylsilanethiolato)-1:2kappa4S:S;2:3kappa4S:S-bis(triisopropylsilanethiolato)-1kappaS,3kappaS-trizinc(II).

The title compound, [Zn(3)(C(9)H(21)SiS)(6)] or [((i)Pr(3)SiS)Zn(mu-SSi(i)Pr(3))(2)Zn(mu-SSi(i)Pr(3))(2)Zn(SSi(i)Pr(3))], is the first structurally characterized homoleptic silanethiolate complex of zinc. A near-linear arrangement of three Zn(II) ions is observed, the metals at the ends being three-coordinate with one terminally bound silanethiolate ligand. The central Zn(II) ion is four-coordinate and tetrahedral, with two bridging silanethiolate ligands joining it to each of the two peripheral Zn(II) ions. The nonbonding intermetallic distances are 3.1344 (11) and 3.2288 (12) A, while the Zn...Zn...Zn angle is 172.34 (2) degrees. A trimetallic silanethiolate species of this type has not been previously identified by X-ray crystallography for any element.