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Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model's predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion. [ABSTRACT FROM AUTHOR]

Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements. [ABSTRACT FROM AUTHOR]

To treat and manage chronic diseases, it is necessary to continuously monitor relevant biomarkers and modify treatment as the disease state changes. Compared to other bodily fluids, interstitial skin fluid (ISF) is a good choice for identifying biomarkers because it has a molecular composition most similar to blood plasma. Herein, a microneedle array (MNA) is presented to extract ISF painlessly and bloodlessly. The MNA is made of crosslinked poly(ethylene glycol) diacrylate (PEGDA), and an optimal balance of mechanical properties and absorption capability is suggested. Besides, the effect of needles' cross-section shape on skin penetration is studied. The MNA is integrated with a multiplexed sensor that provides a color change in a biomarker concentration-dependent manner based on the relevant reactions for colorimetric detection of pH and glucose biomarkers. The developed device enables diagnosis by visual inspection or quantitative red, green, and blue (RGB) analysis. The outcomes of this study show that MNA can successfully identify biomarkers in interstitial skin fluid in a matter of minutes. The home-based long-term monitoring and management of metabolic diseases will benefit from such practical and self-administrable biomarker detection. [ABSTRACT FROM AUTHOR]

Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH. [ABSTRACT FROM AUTHOR]

Tumour drug delivery using nanocarriers is attracting ample attentions due to their high drug-loading capacity. Regarding specific tumour microenvironment properties as acidic pH, smart nanocarriers with the ability of responding to the microenvironment, can have a profound effect on the level of drug release and subsequent tumour treatment. In this study, by combining the advantages of multiwall carbon nanotube and pH-sensitive nanogels, multifunctional magneto/pH-responsive nano-hybrid system is developed to deliver the doxorubicin as a general cancer chemotherapeutic drug. The chemical and physical properties of the nanocarrier, as well as drug-loading efficiency and drug releasing characteristics were analysed. It was showed functionalized CNT has low pH-responsiveness in acidic environment, whereas chitosan-coated magnetic nanocomposite can result in greater pH-responsiveness and subsequently higher drug release over a week compared to nanocomposite system without chitosan. This behaviour was proved in Live/Dead assay of the U-87 glioblastoma cell lines exposed to DOX release supernatant at different time intervals so that significant effect of DOX supernatant on cancer cell proliferation suppression was showed. [ABSTRACT FROM AUTHOR]

Tumor spheroid formation in microwell arrays is a promising approach for high-throughput screening of chemotherapeutic agents. This method offers the advantage of better mimicking the complexities of tumors as compared to conventional monolayer culture systems. However, using these technologies to their full potential is hindered by the inability to seed the cells within the wells uniformly and with high yield and reproducibility. Moreover, standard manufacturing approaches for fabrication of microwell arrays rely on lithography and etching techniques, which are costly, labor-intensive, and time-consuming. Herein, we report on the development of self-filling microwell arrays (SFMAs) in which cells are directed from a loading chamber to microwells using inclined guiding channels. The SFMAs are fabricated by replica molding of three-dimensionally (3D) printed molds in agarose. We characterize the fabrication process, demonstrate the ability to culture breast adenocarcinoma MCF-7 and glioma U87 in SFMAs and perform drug toxicity studies. We envision that the proposed innovative approach opens avenues of opportunities for high-throughput three-dimensional cell culture for drug screening and disease modeling. [ABSTRACT FROM AUTHOR]

The effects of adding Al2O3 nanoparticles on the microstructure, tribological, magnetic, and corrosion properties of CuFe-Al2O3 nanocomposites were investigated in this work. The mixture of Cu-25 wt.% Fe powder with 5 vol.% Al2O3 was mechanically milled. X-ray diffraction results revealed that after 60 h of mechanical alloying, CuFe solid solution was formed. Magnetic hysteresis loops of the mechanically alloyed powders were extracted at room temperature. The morphology and elemental analysis of the sintered specimens were studied by field emission scanning electron microscope (SEM). It was observed that uniform distribution and embedding of Al2O3 nanoparticles in the CuFe alloy matrix in nanocomposites were achieved, which exhibited excellent performances. Tribological properties were evaluated through a pin-on-disk wear test, and it was found that by the addition of Al2O3 nanoparticles to CuFe alloy, the weight loss rate was reduced by 30%. The existence of Al2O3 nanoparticles in the matrix of CuFe alloy causes the wear mechanism change from adhesive to abrasive, which means a considerable wear resistance was obtained in nanocomposites. The corrosion properties of the sintered samples in a solution of 3.5% NaCl were studied by potentiodynamic polarization. With the addition of Al2O3 nanoparticles, the corrosion rate of the alloy was reduced by 75%. [ABSTRACT FROM AUTHOR]

Hyperthermia treatment of different cancers based on magnetic nanoparticles has gained significant attention in recent years. In this work, biocompatible maghemite (γ-Fe2O3) nanorods were synthesized by dehydroxylation of lepidocrocite (γ-FeOOH) nanorods, using hydrolysis of ferrous salts in the presence of urea followed by calcination at 300 °C for 3 h. Maghemite nanospheres were also synthesized by oxidation of co-precipitated magnetite (Fe3O4) nanoparticles, followed by heat treatment at 250 °C for 3 h. The samples were analyzed by X-ray diffraction, vibrating sample magnetometry, and field emission scanning electron microscopy techniques. Cell viability of nanorods and nanospheres before and after applying a magnetic field was studied by MTT assay on G292 cell lines as a candidate of osteosarcoma 2D-cultured model. The heating capacity of the rod-like and spherical magnetic nanoparticles (MNP) was evaluated under a magnetic field using a solid state induction heating equipment. Moreover, the minimal inhibitory concentration (MIC) antibacterial activity of magnetic nanorods and nanospheres was investigated. The results showed that cell proliferation gradually increased in the presence of both maghemite nanorods and nanospheres compared to the control sample. However, cell viability decreased after applying hyperthermia treatment as indicative of cell apoptosis. Quantification of antibacterial properties also showed the MIC behavior of both nanoparticles at a concentration of 0.078 mg/ml. [ABSTRACT FROM AUTHOR]

Alumina nanoparticles were added to CuTiNi alloy to study their effect on microstructure, tribological properties, and corrosion behaviors of the fabricated alloy. A mixture of Cu-20 wt% Ti-10 wt% Ni powder with 0 and 5 wt% alumina was mixed in a high-energy ball mill. Results indicated that CuTiNi solid solution was formed after 40 h of mechanical alloying. Magnetic hysteresis loops of the mechanically alloyed powders were extracted at room temperature. The mechanically alloyed powders were compacted and then conventionally sintered. Tribological properties of sintered samples were evaluated by ball-on-disk wear test. Comparing the wear rate of the nanocomposite with that of CuTiNi alloy indicated that addition of alumina nanoparticles decreased the wear rate by about 40 %. Corrosion behavior of sintered samples studied using cyclic potentiodynamic polarization in 3.5 % NaCl solution revealed that corrosion current density of the nanocomposite was decreased by about 98 % compared to that of CuTiNi alloy. [ABSTRACT FROM AUTHOR]

Cerium containing coatings are interested because of corrosion and wear resistance characteristics, in another point valve metals have the ability to be treated with plasma electrolytic oxidation (PEO). Different cerium sources, from base metal, pretreatment, post treatment and electrolyte are implemented for Mg alloys. In this research Ti substrates was treated via PEO in less studied, cerium chloride containing electrolytes. Effect of cerium ion concentration was studied on morphology, corrosion and wear properties using SEM, FTIR, polarization, EIS, pin on disk experiments. It was observed that cerium participates in coatings slightly and there is an optimum content for cerium ions in electrolytes which results in improved corrosion and wear properties, mostly from modifying coating roughness and morphology. Addition of cerium ions to electrolyte, first decreases and then increases coating roughness and coefficient of friction. [ABSTRACT FROM AUTHOR]

In this study, we used urea and ammonia to synthesize zinc cobalt ferrites via microwave-assisted hydrothermal method from metallic nitrates. It was figured that despite the common synthesis method and equal amount of nitrates, magnetic properties of nanoparticles were different. Changes in magnetic properties are discussed based on factors such as nanoparticles' size, surface atom spins, cationic distribution, magnetocrystalline energy. Nanoparticles synthesized with ammonia showed lower magnetization while higher magnetocrystalline energy and greater coercivity was obtained due to better cationic distribution. It was also revealed that by increasing magnetization, the susceptibility of nanoparticles increases and then declines. [ABSTRACT FROM AUTHOR]

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a rapidly progressive and deadly form of brain tumor with a median survival rate of ~15 months. GBMs are hard to treat and significantly affect the patient's physical and cognitive abilities and quality of life. Temozolomide (TMZ)—an alkylating agent that causes DNA damage—is the only chemotherapy choice for the treatment of GBM. However, TMZ also induces autophagy and causes tumor cell resistance and thus fails to improve the survival rate among patients. Here, we studied the drug-induced programmed cell death and invasion inhibition capacity of TMZ and a mevalonate cascade inhibitor, simvastatin (Simva), in a three-dimensional (3D) microfluidic model of GBM. We elucidate the role of autophagy in apoptotic cell death by comparing apoptosis in autophagy knockdown cells (Atg7 KD) against their scrambled counterparts. Our results show that the cells were significantly less sensitive to drugs in the 3D model as compared to monolayer culture systems. An immunofluorescence analysis confirmed that apoptosis is the mechanism of cell death in TMZ- and Simva-treated glioma cells. However, the induction of apoptosis in the 3D model is significantly lower than in monolayer cultures. We have also shown that autophagy inhibition (Atg7 KD) did not change TMZ and Simva-induced apoptosis in the 3D microfluidic model. Overall, for the first time in this study we have established the simultaneous detection of drug induced apoptosis and autophagy in a 3D microfluidic model of GBM. Our study presents a potential ex vivo platform for developing novel therapeutic strategies tailored toward disrupting key molecular pathways involved in programmed cell death and tumor invasion in glioblastoma. [ABSTRACT FROM AUTHOR]