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Bevacizumab (Bev) a humanized monoclonal antibody that fights vascular endothelial growth factor A (VEGF-A). It was the first specifically considered angiogenesis inhibitor and it has now become the normative first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the current study, polyphenolic compounds were isolated from bee pollen (PCIBP) and encapsulated (EPCIBP) inside moieties of hybrid peptide–protein hydrogel nanoparticles in which bovine serum albumin (BSA) was combined with protamine-free sulfate and targeted with folic acid (FA). The apoptotic effects of PCIBP and its encapsulation (EPCIBP) were further investigated using A549 and MCF-7 cell lines, providing significant upregulation of Bax and caspase 3 genes and downregulation of Bcl2, HRAS, and MAPK as well. This effect was synergistically improved in combination with Bev. Our findings may contribute to the use of EPCIBP simultaneously with chemotherapy to strengthen the effectiveness and minimize the required dose. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- β1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-β1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- β1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

To date, cancer continues to be one of the deadliest diseases. Current therapies are often ineffective, leading to the urgency to develop new therapeutic strategies to improve treatments. Conventional chemotherapeutics are characterized by a reduced therapeutic efficacy, as well as them being responsible for important undesirable side effects linked to their non-specific toxicity. In this context, natural nanomaterials such as clayey mineral nanostructures of various shapes (flat, tubular, spherical and fibrous) with adjustable physico-chemical and morphological characteristics are emerging as systems with extraordinary potential for the delivery of different therapeutic agents to tumor sites. Thanks to their submicron size, high specific surface area, high adsorption capacity, chemical inertia and multilayer organization of 0.7 to 1 nm-thick sheets, they have aroused considerable interest among the scientific community as nano systems that are highly biocompatible in cancer therapy. In oncology, the nano-clays usually studied are halloysite, bentonite, laponite, kaolinite, montmorillonite and sepiolite. These are multilayered minerals that can act as nanocarriers (with a drug load generally between 1 and 10% by weight) for improved stabilization, efficient transport and the sustained and controlled release of a wide variety of anticancer agents. In particular, halloysite, montmorillonite and kaolinite are used to improve the dissolution of therapeutic agents and to delay and/or direct their release. In this review, we will examine and expose to the scientific community the extraordinary potential of nano-clays as unique crystalline systems in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Magnetic Nanoparticles (MNPs) are becoming increasingly popular for biomedical imaging and drug delivery, particularly cancer theranostics. Due to their excellent inherent properties and the accessibility to be tailor-made according to specific requirements, they stand out from the crowd and are close, yet so far. While the number of publications related to MNPs' drug-delivery systems reported in the literature increases yearly, relatively more minor conversion has been observed from the bench to the bedside. It is of paramount importance to understand and work on the shortcomings and redesign the strategies to increase the clinical translatability of MNPs. 'Supply as per Demand' should be followed while designing an MNP-based delivery system. To achieve this, a better understanding of the clinical issues should be addressed early, and downstream methods should be prepared to resolve them. More significantly, all clinical problems in one delivery system should be eliminated, and one problem and one solution should be pursued. This opinion review explores the current limitations in evaluating magnetic nanoparticle performance, suggesting a promising standardized pathway to clinical translation. [ABSTRACT FROM AUTHOR]

Highlights: 1. Resveratrol is an antioxidant and exhibits numerous potential therapeutic applications. However, it suffers from low water-solubility, degradation, and poor bioavailability. The conventional dosage form of resveratrol shows various limitations, such as prolonged therapy, erratic bioavailability, and absence of effective drug concentrations in tissues. 2. Nanocarrier-based delivery systems are being studied extensively to target tissues and cells to improve the therapeutic potential of poorly soluble molecules by enhancing their bioavaila-bility, solubility, and retention time. 3. Resveratrol can act as a potential anti-cancer agent and lowers the progression of cancer disease. Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol, belonging to a group known as stilbenoids (STBs). Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is mainly found in grapes, wine, nuts, and berries. A wide range of biological activities has been demonstrated by resveratrol, including antimicrobial, antioxidant, antiviral, antifungal, and antiaging effects, and many more are still under research. However, as with many other plant-based polyphenol products, resveratrol suffers from low bioavailability once administered in vivo due to its susceptibility to rapid enzyme degradation by the body's innate immune system before it can exercise its therapeutic influence. Therefore, it is of the utmost importance to ensure the best use of resveratrol by creating a proper resveratrol delivery system. Nanomedicine and nanodelivery systems utilize nanoscale materials as diagnostic tools or to deliver therapeutic agents in a controlled manner to specifically targeted locations. After a brief introduction about polyphenols, this review overviews the physicochemical characteristics of resveratrol, its beneficial effects, and recent advances on novel nanotechnological approaches for its delivery according to the type of nanocarrier utilized. Furthermore, the article summarizes the different potential applications of resveratrol as, for example, a therapeutic and disease-preventing anticancer and antiviral agent. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an xenoestrogenic chemical used extensively in the fabrication of baby bottles, reusable plastic water bottles and polycarbonate plastic containers. The current study aims to investigate the hepatoprotective activity of Moringa oleifera Lam leaf extract (MOLE) and hydrogel NPs made of starch-MOLE-Bovine Serum Albumin (BSA) against Bisphenol A-induced liver toxicity in male rats. Fabrication and characterization of hydrogel NPs formed of starch-MOLE-BSA were investigated using FTIR, TEM, zeta potential, UV-visible spectroscopy and fluorescence spectrophotometer. The potential efficacy of hydrogel NPs was studied. Compared to the results of control, the level of liver function, oxidative stress markers and lipid profile status were remodulated in the groups treated with MOLE and hydrogel NPs (Encap. MOLE). Meanwhile, the administration of MOLE and Encap MOLE significantly increased antioxidant activity and decreased the level of apoptotic pathways. Heme oxygenase (HO)-1 and growth arrest -DNA damage-inducible gene 45b (Gadd45b) were also regulated in the groups treated with MOLE and Encap. MOLE compared to the group which received BPA alone. In the present study, MOLE and hydrogel NPs led to remarkable alterations in histological changes during BPA administration. Overall, MOLE has a potential antioxidant activity which can be used in the treatment of liver disorders. [ABSTRACT FROM AUTHOR]

Natural halloysite clay nanotubes (HNTs) are versatile inorganic reinforcing materials for creating hybrid composites. Upon doping HNTs with polymers, coating, or loading them with bioactive molecules, the production of novel nanocomposites is possible, having specific features for several applications. To investigate HNTs composites nanostructures, AFM is a very powerful tool since it allows for performing nano-topographic and morpho-mechanical measurements in any environment (air or liquid) without treatment of samples, like electron microscopes require. In this review, we aimed to provide an overview of recent AFM investigations of HNTs and HNT nanocomposites for unveiling hidden characteristics inside them envisaging future perspectives for AFM as a smart device in nanomaterials characterization. [ABSTRACT FROM AUTHOR]

Calcium carbonate (CaCO3) particles represent an appealing choice as a drug delivery system due to their biocompatibility, biodegradability, simplicity and cost-effectiveness of manufacturing, and stimulus-responsiveness. Despite this, the synthesis of CaCO3 particles with controlled size in the nanometer range via a scalable manufacturing method remains a major challenge. Here, by using a co-precipitation technique, we investigated the impact on the particle size of different synthesis parameters, such as the salt concentration, reaction time, stirring speed, and temperature. Among them, the salt concentration and temperature resulted in having a remarkable effect on the particle size, enabling the preparation of well-dispersed spherical nanoparticles with a size below 200 nm. Upon identification of optimized synthesis conditions, the encapsulation of the antitumoral agent resveratrol into CaCO3 nanoparticles, without significantly impacting the overall size and morphology, has been successfully achieved. [ABSTRACT FROM AUTHOR]

In humans, glioblastoma is the most prevalent primary malignant brain tumor. Usually, glioblastoma has specific characteristics, such as aggressive cell proliferation and rapid invasion of surrounding brain tissue, leading to a poor patient prognosis. The current therapy—which provides a multidisciplinary approach with surgery followed by radiotherapy and chemotherapy with temozolomide—is not very efficient since it faces clinical challenges such as tumor heterogeneity, invasiveness, and chemoresistance. In this respect, natural substances in the diet, integral components in the lifestyle medicine approach, can be seen as potential chemotherapeutics. There are several epidemiological studies that have shown the chemopreventive role of natural dietary compounds in cancer progression and development. These heterogeneous compounds can produce anti-glioblastoma effects through upregulation of apoptosis and autophagy; allowing the promotion of cell cycle arrest; interfering with tumor metabolism; and permitting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis inhibition. Although these beneficial effects are promising, the efficacy of natural compounds in glioblastoma is limited due to their bioavailability and blood–brain barrier permeability. Thereby, further clinical trials are necessary to confirm the in vitro and in vivo anticancer properties of natural compounds. In this article, we overview the role of several natural substances in the treatment of glioblastoma by considering the challenges to be overcome and future prospects. [ABSTRACT FROM AUTHOR]

Furthermore, the delivery of macromolecular drugs can be enhanced by modulating the EPR effect in the targeted tumor tissues by applying adjuvants, inflammatory factors, or antibody photosensitizers [[11], [13]]. 20304019 4 Shi Y., Van Der Meel R., Chen X., Lammers T. The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. 26348965 11 Maeda H. Nitroglycerin enhances vascular blood flow and drug delivery in hypoxic tumor tissues: Analogy between angina pectoris and solid tumors and enhancement of the EPR effect. 20074683 12 Maeda H. The link between infection and cancer: Tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect. [Extracted from the article]

Hydrogel-based polymers are represented by those hydrophilic polymers having functional groups in their chain such as amine (NH2), hydroxyl [-OH], amide (-CONH-, -CONH2), and carboxyl [COOH]. These hydrophilic groups raise their potential to absorb fluids or aqueous solution more than their weights. This physicochemical mechanism leads to increased hydrogel expansion and occupation of larger volume, the process which shows in swelling behavior. With these unique properties, their use for biomedical application has been potentially raised owing also to their biodegradability and biocompatibility. Chitosan as a natural copolymer, presents a subject for hydrogel structures and function. This review aimed to study the structure as well as the function of chitosan and its hydrogel properties. [ABSTRACT FROM AUTHOR]

Hydrogels are widely used materials which have many medical applications. Their ability to absorb aqueous solutions and biological fluids gives them innovative characterizations resulting in increased compatibility with biological activity. In this sense, they are used extensively for encapsulation of several targets such as biomolecules, viruses, bacteria, and mammalian cells. Indeed, many methods have been published which are used in hydrogel formulation and biomedical encapsulations involving several cross-linkers. This system is still rich with the potential of undiscovered features. The physicochemical properties of polymers, distinguished by their interactions with biological systems into mucoadhesive, gastro-adhesive, and stimuli responsive polymers. Hydrogel systems may be assembled as tablets, patches, gels, ointments, and films. Their potential to be co-formulated as nanoparticles extends the limits of their assembly and application. In this review, mucoadhesive nanoparticles and their importance for biomedical applications are highlighted with a focus on mechanisms of overcoming mucosal resistance. [ABSTRACT FROM AUTHOR]

LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a "nano-elastic" carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated. [ABSTRACT FROM AUTHOR]

Glucose consumption in many types of cancer cells, in particular hepatocellular carcinoma (HCC), was followed completely by over-expression of type II hexokinase (HKII). This evidence has been used in modern pharmacotherapy to discover therapeutic target against glycolysis in cancer cells. Bromopyruvate (BrPA) exhibits antagonist property against HKII and can be used to inhibit glycolysis. However, the clinical application of BrPA is mostly combined with inhibition effect for healthy cells particularly erythrocytes. Our strategy is to encapsulate BrPA in a selected vehicle, without any leakage of BrPA out of vehicle in blood stream. This structure has been constructed from chitosan embedded into oleic acid layer and then coated by dual combination of folic acid (FA) and bovine serum albumin (BSA). With FA as specific ligand for cancer folate receptor and BSA that can be an easy binding for hepatocytes, they can raise the potential selection of carrier system. [ABSTRACT FROM AUTHOR]

Gold standard therapies require the use of chemotherapeutic drugs associated with radiotherapy and the surgical excision of the localized tumors. 10.1038/s41586-019-1730-1. 31723286 2 Samadian H., Mohammad-Rezaei R., Jahanban-Esfahlan R., Massoumi B., Abbasian M., Jafarizad A., Jaymand M. A de novo theranostic nanomedicine composed of PEGylated graphene oxide and gold nanoparticles for cancer therapy. Currently, cancer represents a major cause of death in the world, despite all the progress made in developing new therapies. [Extracted from the article]

References 1 De Matteis V., Cascione M., Toma C.C., Pellegrino P., Rizzello L., Rinaldi R. Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles. In addition, the cell viability assessment confirmed the negligible toxicity of these materials in cells. The increasingly widespread use of engineered nanomaterials in many applications increases the need to understand the mechanisms behind their toxicity. [Extracted from the article]

Aim of this work was to investigate the automatic echographic detection of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), by employing an innovative method based on advanced spectral analysis of the corresponding "raw" radiofrequency backscatter signals. Different HNT concentrations in a low range (5.5-66 × 1010 part/mL, equivalent to 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and imaged through a clinically-available echographic device at a conventional ultrasound diagnostic frequency (10 MHz). The most effective response (sensitivity = 60%, specificity = 95%), was found at a concentration of 33 × 1010 part/mL (1.5 mg/mL), representing a kind of best compromise between the need of enough particles to introduce detectable spectral modifications in the backscattered signal and the necessity to avoid the losses of spectral peculiarity associated to higher HNT concentrations. Based on theoretical considerations and quantitative comparisons with literature-available results, this concentration could also represent an optimal concentration level for the automatic echographic detection of different solid nanoparticles when employing a similar ultrasound frequency. Future dedicated studies will assess the actual clinical usefulness of the proposed approach and the potential of HNTs for effective theranostic applications. [ABSTRACT FROM AUTHOR]

Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic® F127 hybrid dendritic–linear–dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2′-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2′-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation. [ABSTRACT FROM AUTHOR]

Crystallization-driven self-assembly (CDSA) of block copolymers bearing one crystallizable block has emerged to be a powerful and highly relevant method for the production of one- and two-dimensional micellar assemblies with controlled length, shape, and corona chemistries. This gives access to a multitude of potential applications, from hierarchical self-assembly to complex superstructures, catalysis, sensing, nanomedicine, nanoelectronics, and surface functionalization. Related to these applications, patchy crystalline-core micelles, with their unique, nanometer-sized, alternating corona segmentation, are highly interesting, as this feature provides striking advantages concerning interfacial activity, functionalization, and confinement effects. Hence, this review aims to provide an overview of the current state of the art with respect to self-assembly concepts, properties, and applications of patchy micelles with crystalline cores formed by CDSA. We have also included a more general discussion on the CDSA process and highlight block-type co-micelles as a special type of patchy micelle, due to similarities of the corona structure if the size of the blocks is well below 100 nm. [ABSTRACT FROM AUTHOR]

Semiconducting polymer nanoparticles (SPN) have been emerging as novel functional nano materials for phototherapy which includes PTT (photo-thermal therapy), PDT (photodynamic therapy), and their combination. Therefore, it is important to look into their recent developments and further explorations specifically in cancer treatment. Therefore, the present review describes novel semiconducting polymers at the nanoscale, along with their applications and limitations with a specific emphasis on future perspectives. Special focus is given on emerging and trending semiconducting polymeric nanoparticles in this review based on the research findings that have been published mostly within the last five years. [ABSTRACT FROM AUTHOR]

This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era. [ABSTRACT FROM AUTHOR]

This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of the addiction risk severity (GARS) test. Based on both neurogenetic and epigenetic evidence, the test evaluates the presence of reward genes and risk alleles. Existing evidence demonstrates that the novel genetic risk testing system can successfully stratify the potential for developing opioid use disorder (OUD) related risks or before initiating opioid analgesic therapy and RDS risk for people in recovery. In the case of opioid use disorders, long-term maintenance agonist treatments like methadone and buprenorphine may create RDS, or RDS may have been in existence, but not recognized. The test will also assess the potential for benefit from medication-assisted treatment with dopamine augmentation. RDS methodology holds a strong promise for reducing the burden of addictive disorders for individuals, their families, and society as a whole by guiding the restoration of dopamine homeostasisthrough anti-reward allostatic neuroadaptations. WC 175. [ABSTRACT FROM AUTHOR]

Over the past decades, there has been a growing interest in using natural molecules with therapeutic potential for biomedical applications. In this context, our aim is focused on anthocyanins (AN) as molecules with anticancer properties that could be used in melanoma local therapies. Due to their susceptibility to environmental changes, current study is based on the design and development of a fluorescent system for carrying and trafficking AN inside melanoma cells. The architectural structure of the proposed system CaCO3(PAH)@RBITC@AN reflects a spherical shape, 1080 nm diameter and a solid groundwork CaCO3(PAH), on which rhodamine B isothiocyanate (RBITC) fluorophore was firstly added; then, poly(acrylic acid) (PAA) polyelectrolytes and poly(allylamine hydrochloride) (PAH) were successfully deposited. Purified AN from chokeberries were entrapped between PAA layers (rate of 94.6%). In vitro tests confirmed that CaCO3(PAH)@RBITC@AN does not affect the proliferation of melanoma B16-F10 cells and proved that their internalization and trafficking can be followed after 24 h of treatment. Data presented here could contribute not only to the existing knowledge about the encapsulation technology of AN but also might bring relevant information for a novel formula to deliver therapeutic molecules or other bio-imaging agents directly into melanoma cells, a strategy that could positively improve tumor therapies. [ABSTRACT FROM AUTHOR]

There is enormous interest in combining two or more nanoparticles for various biomedical applications, especially in anti-cancer agent delivery. In this study, the microsphere nanoparticles were prepared (MSNPs) and their impact on cancer cells was examined. The MSNPs were prepared by using the hydrothermal method where strontium (Sr), barium (Ba), dysprosium (Dy), samarium (Sm), and iron oxide (Fe8−2xO19) were combined, and dysprosium (Dy) and samarium (Sm) was substituted with strontium (Sr) and barium (Ba), preparing Sr0.5Ba0.5DyxSmxFe8−2xO19 (0.00 ≤ x ≤ 1.0) MSNPs. The microspheres were characterized by X-ray powder diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. The diffraction pattern of nanohexaferrites (NHFs) reflected the signature peaks of the hexagonal structure. The XRD revealed a pure hexagonal structure without any undesired phase, which indicated the homogeneity of the products. The crystal size of the nanoparticles were in the range of 22 to 36 nm by Scherrer's equation. The SEM of MSNPs showed a semi-spherical shape with a high degree of aggregation. TEM and HR-TEM images of MSNPs verified the spherical shape morphology and structure that approved an M-type hexaferrite formation. The anti-cancer activity was examined on HCT-116 (human colorectal carcinoma) and HeLa (cervical cancer cells) using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and post-48 h treatment of MSNPs caused a dose-dependent inhibition of HCT-116 and HeLa cell proliferation and growth. Conversely, no significant cytotoxic effect was observed on HEK-293 cells. The treatments of MSNPs also induced cancer cells DNA disintegration, as revealed by 4′,6-diamidino-2-phenylindole (DAPI) staining. Finally, these findings suggest that synthesized MSNPs possess potential inhibitory actions on cancerous cells without harming normal cells. [ABSTRACT FROM AUTHOR]

This research reports the influence of polar monomer contents in ethylene vinyl acetate copolymer (EVA) and ethylene vinyl alcohol copolymer (EVOH) on the morphology, mechanical and barrier properties of polypropylene/ethylene copolymer (PP) reinforced with organically modified montmorillonite (MMT). PP/EVA and PP/EVOH (75/25 wt %) blends were reinforced with 3 wt % MMT in an internal mixer system. Samples were compression-molded into films of 300   μ m . The structural characterization was made using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the mechanical properties were obtained by tension tests and the barrier properties by oxygen transmission rate (OTR). XRD patterns showed a combination of intercalated/exfoliated morphologies for the MMT, with higher d-001 interplanar distance increments for the blends with higher content of polar functional groups. SEM and TEM micrographs complement the results of the XRD analysis and show differences in the morphologies depending on the miscibility of the polyolefin and the polar monomer copolymer. Mechanical properties and oxygen permeability of composites exhibited a higher improvement, by the addition of MMT, for higher intermolecular interactions and most miscible polymeric system of the EVA. These results show that the higher the number of interactions, given by the VA or OH polar functional groups, the morphology and the miscibility between polyolefin and copolymer imply dispersion improvements of the nanocomposites and, in consequence, a higher improvement on the mechanical and barrier properties of the composite material. [ABSTRACT FROM AUTHOR]

This work applies a multi-scale approach to the microencapsulation by interfacial polymerization. Such microencapsulation is used to produce fertilizers, pesticides and drugs. In this study, variations at three different scales (molecular, microscopic and macroscopic) of product design (i.e., product variables, process variables and properties) are considered simultaneously. We quantify the effect of the formulation, composition and pH change on the microcapsules' properties. Additionally, the method of measuring the strength of the microcapsules by crushing a sample of microcapsules' suspension was tested. Results show that the xylene release rate in the microcapsules decreases when the amine functionality is greater due to a stronger crosslinking. Such degree of crosslinking increases the compression force over the microcapsules and improves their appearance. When high levels of amine concentration are used, the initial pH values in the reaction are also high which leads to agglomeration. This study provides a possible explanation to the aggregation based on the kinetic and thermodynamic controls in reactions and shows that the pH measurements account for the polyurea reaction and carbamate formation, which is a reason why this is not a suitable method to study kinetics of polymerization. Finally, the method used to measure the compressive strength of the microcapsules detected differences in formulations and composition with low sensibility. [ABSTRACT FROM AUTHOR]

Cellulose nanocrystals (CNCs) and/or sepiolite (SPT) were thermomechanically mixed with un-plasticised chitosan and chitosan/carboxymethyl cellulose (CMC) blends plasticised with 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]). Examination of the morphology of these materials indicates that SPT aggregates were reduced when CNCs or [C2mim][OAc] were present. Inclusion of CNCs and/or SPT had a greater effect on material properties when the matrices were un-plasticised. Addition of SPT or CNCs altered the crystalline structure of the un-plasticised chitosan matrix. Moreover, a combination of SPT and CNCs was more effective at suppressing re-crystallisation. Nonetheless, the mechanical properties and surface hydrophobicity were more related to CNC/SPT–biopolymer interactions. The un-plasticised bionanocomposites generally showed increased relaxation temperatures, enhanced tensile strength, and reduced surface wettability. For the [C2mim][OAc] plasticised matrices, the ionic liquid (IL) dominates the interactions with the biopolymers such that the effect of the nanofillers is diminished. However, for the [C2mim][OAc] plasticised chitosan/CMC matrix, CNCs and SPT acted synergistically suppressing re-crystallisation but resulting in increased tensile strength. [ABSTRACT FROM AUTHOR]

The introduction of nanoparticles made of polymers, protein, and lipids as drug delivery systems has led to significant progress in modern medicine. Since the application of nanoparticles in medicine involves the use of biodegradable, nanosized materials to deliver a certain amount of chemotherapeutic agents into a tumor site, this leads to the accumulation of these nanoencapsulated agents in the right region. This strategy minimizes the stress and toxicity generated by chemotherapeutic agents on healthy cells. Therefore, encapsulating chemotherapeutic agents have less cytotoxicity than non-encapsulation ones. The purpose of this review is to address how nanoparticles made of polymers and lipids can successfully be delivered into lung cancer tumors. Lung cancer types and their anatomies are first introduced to provide an overview of the general lung cancer structure. Then, the rationale and strategy applied for the use of nanoparticle biotechnology in cancer therapies are discussed, focusing on pulmonary drug delivery systems made from liposomes, lipid nanoparticles, and polymeric nanoparticles. Many nanoparticles fabricated in the shape of liposomes, lipid nanoparticles, and polymeric nanoparticles are summarized in our review, with a focus on the encapsulated chemotherapeutic molecules, ligand–receptor attachments, and their targets. Afterwards, we highlight the nanoparticles that have demonstrated promising results and have been delivered into clinical trials. Recent clinical trials that were done for successful nanoparticles are summarized in our review. [ABSTRACT FROM AUTHOR]

Transforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone to move into the metastatic process. This finding has received great attention for discovering new therapeutic molecules against the TGFβ1 pathway. Among many TGFβ1 inhibitors, peptides (P17 and P144) were designed to block the TGFβ1 pathway. However, their therapeutic applications have limited use, due to lack of selection for their targets and their possible recognition by the immune system and further due to their potential cytotoxicity on healthy cells. Besides that, P144 is a highly hydrophobic molecule with less dissolution even in organic solution. Here, we aimed to overcome the dissolution of P144, as well as design nano-delivery strategies to protect normal cells, to increase cellular penetration and to raise the targeted therapy of both P17 and P144. Peptides were encapsulated in moieties of polymer hybrid protein. Their assembly was investigated by TEM, microplate spectrum analysis and fluorescence microscopy. SMAD phosphorylation was analyzed by Western blot as a hallmark of their biological efficiency. The results showed that the encapsulation of P17 and P144 might improve their potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta (TGF-β) is a pleiotropic cytokine with dual role in hepatocellular carcinoma (HCC). It acts as tumor-suppressor and tumor-promoter in the early and late stage respectively. TGF-β influences the tumor-stroma cross-talk affecting the tumoral microenvironment. Therefore, inhibiting the TGF- β mediated pathway alone and/or in combination with chemotherapeutics represents an important therapeutic option. Experimental models to dissect the role of TGF-β in HCC tumor progression as well as the effectiveness of specific inhibitors are tricky. HCC cell lines respond to TGF-β according to their epithelial phenotype. However, the mesenchymal and more aggressive HCC cell lines in vitro, do not develop tumors when transplanted in vivo, thus hampering the understanding of molecular pathways that dictate outcome. In addition, in this model the native immune system is abolished, therefore the contribution of inflammation in hepatocarcinogenesis is unreliable. Different strategies have been set up to engineer HCC animal models, including genetically modified mice, chemically induced HCC, or hydrodynamic techniques. Patient-derived xenograft is currently probably the most fascinating model, keeping in mind that models cannot mirror all the reality. In this context, we discuss the different available HCC mouse models including our experimental model treated with inhibitor of TGF-β receptor Type I kinase (Galunisertib) and a potential role of exosomes in TGF-β moderated tumor progression of HCC. Unfortunately, no positive results were obtained in our treated orthotopic model because it does not reproduce the critical tumor-stroma interactions of the HCC. [ABSTRACT FROM AUTHOR]

The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order to fully understand the cytotoxic mechanisms. In this regard, we have evaluated the morphomechanical alteration in human breast adenocarcinoma cell line (MCF-7) exposed to TiO2NPs at two different concentrations (25 and 50 µg/mL) and two time points (24 and 48 h). By using confocal and atomic force microscopy, we demonstrated that TiO2NP exposure induces significant alterations in cellular membrane elasticity, due to actin proteins rearrangement in cytoskeleton, as calculated in correspondence to nuclear and cytoplasmic compartments. In this work, we have emphasized the alteration in mechanical properties of the cellular membrane, induced by nanoparticle exposure. [ABSTRACT FROM AUTHOR]

Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine simultaneous variations of Young's modulus, the maximum adhesion force, and tether formation, thereby determining cell motility and adhesiveness. Effects of treatment were measured at several time-points (0–6 h, 24 h, and 48 h); longer exposures resulted in cell death. Our results demonstrated that AFM can be efficiently used as a diagnostic tool to monitor irreversible morpho/nano-mechanical changes in cancer cells during the early steps of drug treatment. [ABSTRACT FROM AUTHOR]

Lauric acid is a green derivate that is abundant in some seeds such as coconut oil where it represents the most relevant fatty acid. Some studies have emphasized its anticancer effect due to apoptosis induction. In addition, the lauric acid is a Phase Change Material having a melting temperature of about 43.2 °C: this property makes it a powerful tool in cancer treatment by hyperthermal stress, generally induced at 43 °C. However, the direct use of lauric acid can have some controversial effects, and it can undergo degradation phenomena in the extracellular environment. For this reason, we have encapsulated lauric acid in a silica shell with a one-step and reproducible synthetic route in order to obtain a monodispersed SiO2@LA NPs with a good encapsulation efficiency. We have used these NPs to expose breast cancer cell lines (MCF-7) at different concentrations in combination with hyperthermal treatment. Uptake, viability, oxidative stress induction, caspases levels, and morphometric parameters were analyzed. These nanovectors showed double action in anticancer treatments thanks to the synergic effect of temperature and lauric acid activity. [ABSTRACT FROM AUTHOR]

The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithelial cells acquiring a mesenchymal-like phenotype. It is widely demonstrated that EMT is linked to tumor progression and metastasis. The transforming growth factor (TGF)-β pathways have been widely investigated, but its role in the hepatocarcinoma EMT is still unclear. While the biochemical pathways have been extensively studied, the alteration of biomechanical behavior correlated to cellular phenotype and motility is not yet fully understood. To better define the involvement of TGF-β1 in the metastatic progression process in different hepatocarcinoma cell lines (HepG2, PLC/PRF/5, HLE), we applied a systematic morphomechanical approach in order to investigate the physical and the structural characteristics. In addition, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, from a biomechanical point of view, using Atomic Force and Confocal Microscopy. Our approach allows for validation of biological data, therefore it may be used in the future as a diagnostic tool to be combined with conventional biomolecular techniques. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) remains an unmet challenge in chemotherapy. Stimuli-responsive nanocarriers emerge as a promising tool to overcome MDR. Herein, pH-sensitive poly(β-amino ester)s polymers (PHP)-based micellar nanoparticles were synthesized for enhanced doxorubicin (DOX) delivery in drug resistant breast cancer MCF-7/ADR cells. DOX-loaded PHP micelles showed rapid cell-internalization and lysosomal escape in MCF-7/ADR cells. The cytotoxicity assays showed relatively higher cell inhibition of DOX-loaded PHP micelles than that of free DOX against MCF-7/ADR cells. Further mechanistic studies showed that PHP micelles were able to inhibit P-glycoprotein (P-gp) activity by lowering mitochondrial membrane potentials and ATP levels. These results suggested that the enhanced antitumor effect might be attributed to PHP-mediated lysosomal escape and drug efflux inhibition. Therefore, PHP would be a promising pH-responsive nanocarrier for enhanced intracellular drug delivery and overcoming MDR in cancer cells. [ABSTRACT FROM AUTHOR]

Micelles as colloidal suspension have attracted considerable attention due to their potential use for both cancer diagnosis and therapy. These structures have proven their ability to deliver poorly water-soluble anticancer drugs, improve drug stability, and have good penetration and site-specificity, leading to enhance therapeutic efficacy. Micelles are composed of hydrophobic and hydrophilic components assembled into nanosized spherical, ellipsoid, cylindrical, or unilamellar structures. For their simple formation, they are widely studied, either by using opposite polymers attachment consisting of two or more block copolymers, or by using fatty acid molecules that can modify themselves in a rounded shape. Recently, hybrid and responsive stimuli nanomicelles are formed either by integration with metal nanoparticles such as silver, gold, iron oxide nanoparticles inside micelles or by a combination of lipids and polymers into single composite. Herein, through this special issue, an updated overview of micelles development and their application for cancer therapy will be discussed. [ABSTRACT FROM AUTHOR]

The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells to acquire an invasive phenotype. The role of transforming growth factor-β1 (TGF-β1) in EMT is still debated. We used confocal laser scanning microscopy and scanning force spectroscopy to perform a morphomechanical analysis on epithelial breast cancer cells (MCF-7), comparing them before and after TGF-β1 exogenous stimulation (5 ng/mL for 48 h). After TGF-β1 treatment, loss of cell–cell adherence (mainly due to the reduction of E-cadherin expression of about 24%) and disaggregation of actin cortical fibers were observed in treated MCF-7. In addition, TGF-β1 induced an alteration of MCF-7 nuclei morphology as well as a decrease in the Young’s modulus, owing to a rearrangement that involved the cytoskeletal networks and the nuclear region. These relevant variations in morphological features and mechanical properties, elicited by TGF-β1, suggested an increased capacity of MCF-7 to migrate, which was confirmed by a wound healing assay. By means of our biophysical approach, we highlighted the malignant progression of breast cancer cells induced by TGF-β1 exposure. We are confirming TGF-β1’s role in EMT by means of morphomechanical evidence that could represent a turning point in understanding the molecular mechanisms involved in cancer progression. [ABSTRACT FROM AUTHOR]

The large use of nanomaterials in many fields of application and commercial products highlights their potential toxicity on living organisms and the environment, despite their physico-chemical properties. Among these, silver nanoparticles (Ag NPs) are involved in biomedical applications such as antibacterial agents, drug delivery vectors and theranostics agents. In this review, we explain the common synthesis routes of Ag NPs using physical, chemical, and biological methods, following their toxicity mechanism in cells. In particular, we analyzed the physiological cellular pathway perturbations in terms of oxidative stress induction, mitochondrial membrane potential alteration, cell death, apoptosis, DNA damage and cytokines secretion after Ag NPs exposure. In addition, their potential anti-cancer activity and theranostic applications are discussed. [ABSTRACT FROM AUTHOR]

The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order to fully understand the cytotoxic mechanisms. In this regard, we have evaluated the morphomechanical alteration in human breast adenocarcinoma cell line (MCF-7) exposed to TiO 2 NPs at two different concentrations (25 and 50 µg/mL) and two time points (24 and 48 h). By using confocal and atomic force microscopy, we demonstrated that TiO 2 NP exposure induces significant alterations in cellular membrane elasticity, due to actin proteins rearrangement in cytoskeleton, as calculated in correspondence to nuclear and cytoplasmic compartments. In this work, we have emphasized the alteration in mechanical properties of the cellular membrane, induced by nanoparticle exposure.

The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithelial cells acquiring a mesenchymal-like phenotype. It is widely demonstrated that EMT is linked to tumor progression and metastasis. The transforming growth factor (TGF)-β pathways have been widely investigated, but its role in the hepatocarcinoma EMT is still unclear. While the biochemical pathways have been extensively studied, the alteration of biomechanical behavior correlated to cellular phenotype and motility is not yet fully understood. To better define the involvement of TGF-β1 in the metastatic progression process in different hepatocarcinoma cell lines (HepG2, PLC/PRF/5, HLE), we applied a systematic morphomechanical approach in order to investigate the physical and the structural characteristics. In addition, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, from a biomechanical point of view, using Atomic Force and Confocal Microscopy. Our approach allows for validation of biological data, therefore it may be used in the future as a diagnostic tool to be combined with conventional biomolecular techniques., Competing Interests: The authors declare no conflict of interest.