Physicochemical Properties Of Nanoparticles Research Articles

Silver nanoparticles biosynthesized from secondary metabolite producing marine actinobacteria and evaluation of their biomedical potential.

Biosynthesis of silver nanoparticles (AgNPs) from marine actinobacteria offers a promising avenue for exploring bacterial extracts as reducing and stabilizing agents. We report extracellular extracts of Rhodococcus rhodochrous (MOSEL-ME29) and Streptomyces sp. (MOSEL-ME28), identified by 16S rRNA gene sequencing for synthesis of AgNPs. Ultrafine silver nanoparticles were biosynthesized using the extracts of R. rhodochrous and Streptomyces sp. and their possible therapeutic applications were studied. The physicochemical properties of nanoparticles were established by HR-SEM/TEM, SAED, UV-Vis, EDS, XRD, and FTIR. UV-Vis spectra displayed characteristic absorption at 430nm and 412nm for AgNPs from Streptomyces sp. (S-AgNPs) and Rhodococcus sp. (R-AgNPs), respectively. HR-SEM/TEM, XRD, EDS analysis confirmed the spherical shape, crystalline nature, and elemental formation of silver. Crystallite or grain size was deduced as 5.52nm for R-AgNPs and 35nm for S-AgNPs. Zeta-potential indicated electrostatic negative charge for AgNPs, while FTIR revealed the presence of diverse functional groups. Disc diffusion assay indicated the broad-spectrum antibacterial potential of S-AgNPs with the maximum inhibition of B. subtilis while R-AgNPs revealed potency against P. aeruginosa at 10µg/mL concentration. Biogenic AgNPs revealed antileishmanial activity and the IC50 was calculated as 164µg/mL and 184µg/mL for R-AgNPs and S-AgNPs respectively. Similarly, the R-AgNPs and S-AgNPs revealed anti-cancer potential against HepG2 and the IC50 was calculated as 49µg/mL and 69µg/mL for R-AgNPs and S-AgNPs, respectively. Moreover, the antioxidant activity showed significant results. MTT assay on RD cells, L20B cells, and Hep-2C indicated intensification in viability by reducing the concentration of R-AgNPs and S-AgNPs. The R-AgNPs and S-AgNPs inhibited sabin-like poliovirus (1TCID50 infection in RD cells). Furthermore, hemocompatibility at low concentrations has been confirmed. Hence, it is concluded that biogenic-AgNPs has the potential to be used in diverse biological applications and that the marine actinobacteria are an excellent resource for fabrication of AgNPs.

The effects of ionic strength and pH on antibacterial activity of hybrid biosurfactant‐biopolymer nanoparticles

AbstractThe physicochemical properties of nanoparticles (NPs) directly influence the colloidal stability and bio‐nano interface, which makes the study of these factors extremely important for NPs applicability. Here, we report the influence of pH and ionic strength in the size, surface charge, and antimicrobial activity of chitosan/rhamnolipid nanoparticles (C/RL‐NPs), synthesized by mixing C and RL in the proportion of 1:1, with the dropwise addition of TPP (sodium tripolyphosphate) in the molar ratio of 1:2.5:1.3, respectively. The obtained NPs were resuspended in different solvents to investigate the ionic strength effect on their stability and antimicrobial activity. By decreasing pH and ionic strength, NPs size was reduced while their surface charge increased. Chitosan nanoparticles (C‐NPs) remained stable in the presence of TPP at acidic pH and low ionic strength, indicating that the modulation of physicochemical conditions for the crosslinking between the two ionic components was an efficient approach to enhance C/RL‐NPs colloidal stability. Thermogravimetric analysis confirmed the interaction between rhamnolipid and chitosan in C/RL‐NPs. The antibacterial activity of C/RL‐NPs against Staphylococcus aureus increased significantly, demonstrating the importance of investigating size and surface charge to dictate the bioactivity properties of such hybrid natural‐based nanomaterial.

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro.

The incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable challenge, as their reactivity and variable behavior have given rise to discrepancies between standard cell-based in vitro and animal in vivo models. In this study, enhanced in vitro models were generated that retained the advantages of traditional cell cultures, but incorporated the modifications of (1) inclusion of an activated immune element and (2) the presence of physiologically-relevant dynamic flow. Following verification that the human alveolar epithelial and macrophage (A549/U937) co-culture could be successfully sustained under both static and dynamic conditions, these cultures, in addition to a standard A549 static model, were challenged with 10 nm citrate coated silver NPs (AgNPs). This work identified a reshaping of the AgNP-cellular interface and differential biological responses following exposure. The presence of dynamic flow modified cellular morphology and reduced AgNP deposition by approximately 20% over the static exposure environments. Cellular toxicity and stress endpoints, including reactive oxygen species, heat shock protein 70, and secretion of pro-inflammatory cytokines, were found to vary as a function of both cellular composition and flow conditions; with activated macrophages and fluid flow both mitigating the severity of AgNP-dependent bioeffects. This work highlights the possibility of enhanced in vitro systems to assess the safety of engineered NPs and demonstrates their effectiveness in elucidating novel NP-cellular interactions and toxicological profiles.

The Impact of Graphite Oxide Nanocomposites on the Antibacterial Activity of Serum.

Nanoparticles can interact with the complement system and modulate the inflammatory response. The effect of these interactions on the complement activity strongly depends on physicochemical properties of nanoparticles. The interactions of silver nanoparticles with serum proteins (particularly with the complement system components) have the potential to significantly affect the antibacterial activity of serum, with serious implications for human health. The aim of the study was to assess the influence of graphite oxide (GO) nanocomposites (GO, GO-PcZr(Lys)2-Ag, GO-Ag, GO-PcZr(Lys)2) on the antibacterial activity of normal human serum (NHS), serum activity against bacteria isolated from alveoli treated with nanocomposites, and nanocomposite sensitivity of bacteria exposed to serum in vitro (using normal human serum). Additionally, the in vivo cytotoxic effect of the GO compounds was determined with application of a Galleria mellonella larvae model. GO-PcZr(Lys)2, without IR irradiation enhance the antimicrobial efficacy of the human serum. IR irradiation enhances bactericidal activity of serum in the case of the GO-PcZr(Lys)2-Ag sample. Bacteria exposed to nanocomposites become more sensitive to the action of serum. Bacteria exposed to serum become more sensitive to the GO-Ag sample. None of the tested GO nanocomposites displayed a cytotoxicity towards larvae.

Nano-SAR Modeling for Predicting the Cytotoxicity of Metal Oxide Nanoparticles to PaCa2.

Nowadays, the impact of engineered nanoparticles (NPs) on human health and environment has aroused widespread attention. It is essential to assess and predict the biological activity, toxicity, and physicochemical properties of NPs. Computation-based methods have been developed to be efficient alternatives for understanding the negative effects of nanoparticles on the environment and human health. Here, a classification-based structure-activity relationship model for nanoparticles (nano-SAR) was developed to predict the cellular uptake of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2). The norm index descriptors were employed for describing the structure characteristics of the involved nanoparticles. The Random forest algorithm (RF), combining with the Recursive Feature Elimination (RFE) was employed to develop the nano-SAR model. The resulted model showed satisfactory statistical performance, with the accuracy (ACC) of the test set and the training set of 0.950 and 0.966, respectively, demonstrating that the model had satisfactory classification effect. The model was rigorously verified and further extensively compared with models in the literature. The proposed model could be reasonably expected to predict the cellular uptakes of nanoparticles and provide some guidance for the design and manufacture of safer nanomaterials.

Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles.

Among various immunotherapies, natural killer (NK) cell cancer immunotherapy using adoptive transfer of NK cells takes a unique position by targeting tumor cells that evade the host immune surveillance. As the first-line innate effector cell, it has been revealed that NK cells have distinct mechanisms to both eliminate cancer cells directly and amplify the anticancer immune system. Over the last 40 years, NK cell cancer immunotherapy has shown encouraging reports in pre-clinic and clinic settings. In total, 288 clinical trials are investigating various NK cell immunotherapies to treat hematologic and solid malignancies in 2021. However, the clinical outcomes are unsatisfying, with remained challenges. The major limitation is attributed to the immune-suppressive tumor microenvironment (TME), low activity of NK cells, inadequate homing of NK cells, and limited contact frequency of NK cells with tumor cells. Innovative strategies to promote the cytolytic activity, durable persistence, activation, and tumor-infiltration of NK cells are required to advance NK cell cancer immunotherapy. As maturing nanotechnology and nanomedicine for clinical applications, there is a greater opportunity to augment NK cell therapeutic efficacy for the treatment of cancers. Active molecules/cytokine delivery, imaging, and physicochemical properties of nanoparticles are well equipped to overcome the challenges of NK cell cancer immunotherapy. Here, we discuss recent clinical trials of NK cell cancer immunotherapy, NK cell cancer immunotherapy challenges, and advances of nanoparticle-mediated NK cell therapeutic efficacy augmentation.

An experimental and computational study to evaluation of chitosan/gum tragacanth coated-natural lipid-based nanocarriers for sunitinib delivery

This study aimed to introduce two natural lipids including the fat tail (FT) and the local oil (Roghan Kermanshahi) in order to design lipid nanocarriers for loading of sunitinib malate as a poorly water-soluble anticancer drug. The drug-loaded solid lipid nanoparticles (SLNs) were fabricated using the modified solvent evaporation-ultrasonic combination method. Coating with chitosan and gum tragacanth (GT) was performed. The physicochemical properties of nanoparticles were analyzed by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC) and scanning electron microscopy (SEM). Also, in vitro drug release and cytotoxicity effect was investigated. Furthermore, the atomic details of SLNs formation and drug encapsulation were investigated by the computational study. The results showed that polymer-FT-SLNs and polymer-Roghan-SLNs had the particle size in the nanometer range (below 150 nm) with the zeta potential values of higher than |−28 mV| and possessed high entrapment efficiency and loading content of sunitinib. The release of drugs from as prepared delivery systems has demonstrated a sustained release pattern, which was fitted to Higuchi’s kinetics. Prepared free SLNs had shown no cytotoxicity effect while sunitinib loaded SLNs had suitable cytotoxicity against acute myeloid leukemia cells (THP-1). The computational approach has demonstrated that the drug-lipid binding energies are higher in the FT system than RK. Our results indicated that the as-prepared chitosan/tragacanth encapsulated natural lipid SLNs can be a good drug nanocarrier for the hydrophobic anticancer drug.

Stabilin-1 is required for the endothelial clearance of small anionic nanoparticles

Clearance of nanoparticles (NPs) after intravenous injection – mainly by the liver – is a critical barrier for the clinical translation of nanomaterials. Physicochemical properties of NPs are known to influence their distribution through cell-specific interactions; however, the molecular mechanisms responsible for liver cellular NP uptake are poorly understood. Liver sinusoidal endothelial cells and Kupffer cells are critical participants in this clearance process. Here we use a zebrafish model for liver-NP interaction to identify the endothelial scavenger receptor Stabilin-1 as a non-redundant receptor for the clearance of small anionic NPs. Furthermore, we show that physiologically, Stabilin-1 is required for the removal of bacterial lipopolysaccharide (LPS/endotoxin) from circulation and that Stabilin-1 cooperates with its homolog Stabilin-2 in the clearance of larger (~100 nm) anionic NPs. Our findings allow optimization of anionic nanomedicine biodistribution and targeting therapies that use Stabilin-1 and -2 for liver endothelium-specific delivery.

Comparative cytotoxicity of kaolinite, halloysite, multiwalled carbon nanotubes and graphene oxide

This study aimed at comparative examining of the interactions between conventionally used clay and carbon nanomaterials and human lung adenocarcinoma cells (A549 cells). The following platy and tubular nanomaterials were tested: carbon nanoparticles, i.e. multi-walled carbon nanotubes (MWCNTs) and graphene oxide nanosheets (GO) as well as nanoclays, i.e. halloysite nanotubes (HNTs) and kaolinite nanosheets (Kaol). Nanoparticle physicochemical properties and their internalization into cells were examined using dynamic light scattering as well as atomic force, 3D laser scanning confocal and darkfield hyperspectral microscopies. Biological aspects of the nanomaterial-cell interaction included assessment of cellular toxicity, DNA damage, metabolic activity, and physical parameters of the cells. Regardless of a shape, carbon nanomaterials demonstrated cell surface adsorption, but negligible penetration into cells compared to nanoclays. However, carbon nanomaterials were found to be the most toxic for cells as probed by the MTS assay. They also turned out to be the most genotoxic for cells compared to nanoclays as revealed by the DNA-Comet assay. GO significantly increased the fraction of apoptotic cells and was the most cytotoxic and genotoxic nanomaterial. Comparison of flow cytometry and MTS data indicated that a cytotoxic effect of MWCNTs was not associated with increased cell death, but was rather due to a decrease in cell metabolic activity and/or proliferation. Finally, no significant effect of the shape of the tested nanomaterials on their internalization and cytotoxicity was revealed.

Nanometals-Containing Polymeric Membranes for Purification Processes.

A recent trend in the field of membrane research is the incorporation of nanoparticles into polymeric membranes, which could produce synergistic effects when using different types of materials. This paper discusses the effect of the introduction of different nanometals such as silver, iron, silica, aluminum, titanium, zinc, and copper and their oxides on the permeability, selectivity, hydrophilicity, conductivity, mechanical strength, thermal stability, and antiviral and antibacterial properties of polymeric membranes. The effects of nanoparticle physicochemical properties, type, size, and concentration on a membrane’s intrinsic properties such as pore morphology, porosity, pore size, hydrophilicity/hydrophobicity, membrane surface charge, and roughness are discussed, and the performance of nanocomposite membranes in terms of flux permeation, contaminant rejection, and antifouling capability are reviewed. The wide range of nanocomposite membrane applications including desalination and removal of various contaminants in water-treatment processes are discussed.

Improved anticancer efficiency of Mitoxantrone by Curcumin loaded PLGA nanoparticles targeted with AS1411 aptamer

Objective(s): Mitoxantrone (MTX) is one of the most commonly used chemotherapeutic agents for treatment of different cancers. However, prolonged treatment with MTX results in unwanted side effects and drug resistant cancer cells. Combination therapies and exploiting of targeted nanoparticles have the potential of improving the efficiency of drug treatment as well as reducing the side effects. Curcumin (CUR) is a biological molecules with anticancer property. In this study, we investigated whether targeted PLGA (Poly Lactic-co-Glycolic Acid)–CUR nanoparticles (NPs) can reinforce the effect of MTX on breast cancer cells.Materials and Methods: PLGA NPs containing CUR targeted with AS1411 aptamer were prepared by single emulsion evaporation method. Physicochemical properties of NPs were investigated. The cytotoxicity of non-targeted and targeted NPs along with MTX was evaluated on MCF7, 4T1 and L929 cell lines. Results: The results showed that PLGA-CUR NPs were synthetized with an average encapsulation efficiency of 66% with a mean size of 186±3.2 nm. The drug release of curcumin from these NPs within 72h was about 59% in neutral medium and 90% in acidic medium. Interestingly, the combined treatment with PLGA-CUR-Apt and MTX inhibited the cancer cell's proliferation significantly more than the non-targeted nanoparticles, CUR and MTX-treated group alone. Conclusion: These results suggest that targeted PLGA-CUR nanoparticles may consider as a potential therapeutic contender in improving the efficacy of MTX in Breast cancer therapy.

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues.

Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo.Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice.Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney.Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo.

Silk Nanoparticle Manufacture in Semi-Batch Format.

Silk nanoparticles have demonstrated utility across a range of biomedical applications, especially as drug delivery vehicles. Their fabrication by bottom-up methods such as nanoprecipitation, rather than top-down manufacture, can improve critical nanoparticle quality attributes. Here, we establish a simple semi-batch method using drop-by-drop nanoprecipitation at the lab scale that reduces special-cause variation and improves mixing efficiency. The stirring rate was an important parameter affecting nanoparticle size and yield (400 < 200 < 0 rpm), while the initial dropping height (5.5 vs 7.5 cm) directly affected nanoparticle yield. Varying the nanoparticle standing time in the mother liquor between 0 and 24 h did not significantly affect nanoparticle physicochemical properties, indicating that steric and charge stabilizations result in high-energy barriers for nanoparticle growth. Manufacture across all tested formulations achieved nanoparticles between 104 and 134 nm in size with high β-sheet content, spherical morphology, and stability in aqueous media for over 1 month at 4 °C. This semi-automated drop-by-drop, semi-batch silk desolvation offers an accessible, higher-throughput platform for standardization of parameters that are difficult to control using manual methodologies.

Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake.

Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure–property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake.

Protein Nanoparticle Charge and Hydrophobicity Govern Protein Corona and Macrophage Uptake.

Protein nanoparticles are biomaterials composed entirely of proteins, with the protein sequence and structure determining the nanoparticle physicochemical properties. Upon exposure to physiological or environmental fluids, it is likely that protein nanoparticles, like synthetic nanoparticles, will adsorb proteins and this protein corona will be dependent on the surface properties of the protein nanoparticles. As there is little understanding of this phenomenon for engineered protein nanoparticles, the purpose of this work was to create protein nanoparticles with variable surface hydrophobicity and surface charge and establish the effect of these properties on the mass and composition of the adsorbed corona, using the fetal bovine serum as a model physiological solution. Albumin, cationic albumin, and ovalbumin cross-linked nanoparticles were developed for this investigation and their adsorbed protein coronas were isolated and characterized by gel electrophoresis and nanoliquid chromatography mass spectrometry. Distinct trends in corona mass and composition were identified for protein nanoparticles based on surface charge and surface hydrophobicity. Proteomic analyses revealed unique protein corona patterns and identified distinct proteins that are known to affect nanoparticle clearance in vivo. Further, the protein corona influenced nanoparticle internalization in vitro in a macrophage cell line. Altogether, these results demonstrate the strong effect protein identity and properties have on the corona formed on nanoparticles made from that protein. This work builds the foundation for future study of protein coronas on the wide array of protein nanoparticles used in nanomedicine and environmental applications.

Silibinin Loaded Solid Lipid Nanoparticles: Effect of Different Lipids and Surfactants on Physicochemical Properties of Nanoparticle

Background: Solid lipid nanoparticles are rapidly developing field of nanotechnology with several potential applications in drug delivery with spherical shape and an average diameter between 1 and 1000 nm. Due to their size and its properties, solid lipid nanoparticles as drug delivery carrier have shown promising potential. Silibinin is a flavonoid with anticancer activity also possesses diverse pharmacologic effects. Methods: Solid lipid nanoparticles of silibinin are prepared by using lipids (Dynasan 114, Glyceryl mono stearate and Compritol 888ATO) with stabilizers (Soy lecithin, Poloxamer 407 and Tween 80). The prepared formulations have been evaluated for Particle size analysis, entrapment efficiency, in-vitro drug release, scanning electron spectroscopy, Fourier transform-infrared studies, Differential scanning calorimetric, X- ray diffraction and Stability study. Results: EE raised with increasing the concentration of surfactants and shows inverse relationship for particle size. The in vitro release profiles of different formulations were studied and showed that sustained release of drug from all formulations. From fitting these data to various statistical models, the Korsmeyer Peppas model was proposed as the best model to describe the statistical indices and mechanism of drug release. DSC and FTIR Shows no interaction between drug and excipients. By SEM Study its shows particles are spherical in shape. Stability studies revealed no prominent changes are seen upon storage. Conclusion: Formulation containing Compritol 888 ATO and Tween 80 (3%) showed prolonged drug release upto 12 hrs, with smaller particle size and narrow particle size distribution, as compared to other formulations with different surfactants and lipids.

Enhanced Cellular Transduction of Nanoparticles Resistant to Rapidly Forming Plasma Protein Coronas.

Nanoparticles (NPs) are increasingly being developed as biomedical platforms for drug/nucleic acid delivery and imaging. However, in biological fluids, NPs interact with a wide range of proteins that form a coating known as protein corona. Coronae can critically influence self-interaction and binding of other molecules, which can affect toxicity, promote cell activation, and inhibit general or specific cellular uptake. Glycosaminoglycan (GAG)-binding enhanced transduction (GET) is developed to efficiently deliver a variety of cargoes intracellularly; employing GAG-binding peptides, which promote cell targeting, and cell penetrating peptides (CPPs) which enhance endocytotic cell internalization. Herein, it is demonstrated that GET peptide coatings can mediate sustained intracellular transduction of magnetic NPs (MNPs), even in the presence of serum or plasma. NP colloidal stability, physicochemical properties, toxicity and cellular uptake are investigated. Using label-free snapshot proteomics, time-resolved profiles of human plasma coronas formed on functionalized GET-MNPs demonstrate that coronae quickly form (<1 min), with their composition relatively stable but evolving. Importantly GET-MNPs present a subtly different corona composition to MNPs alone, consistent with GAG-binding activities. Understanding how NPs interact with biological systems and can retain enhanced intracellular transduction will facilitate novel drug delivery approaches for cell-type specific targeting of new nanomaterials.

RETRACTED: Chitosan-Coated Titanium Dioxide-Embedded Paclitaxel Nanoparticles Enhance Anti-Tumor Efficacy Against Osteosarcoma

ObjectiveTitanium dioxide nanoparticles (TiO2) nanoparticles have been widely explored in the prevention of cancer risk. Due to the difficult solubility of TiO2 nanoparticles, it is essential to synthesize new surfactants to increase its bioavailability and anti-tumor activity and reduce its cytotoxicity. Furthermore, oxidative and inflammation are closely associated with the osteosarcoma risk. Chitosan has biocompatibility, antioxidant and anti-inflammatory properties. The effects of chitosan-coated TiO2-embedded paclitaxel nanoparticles on an osteosarcoma model were explored.MethodsAn osteosarcoma model was established and chitosan-coated TiO2-embedded paclitaxel nanoparticles were prepared using a freeze-drying strategy. The morphological characteristics of nanoparticles were observed using scanning electron microscopy (SEM). The physicochemical properties of nanoparticle were evaluated by X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The cytotoxicity was tested by using human osteoblast cells hFob1.19 and osteosarcoma cells 143B. Osteosarcoma mice were treated with PBS buffer, paclitaxel, TiO2-embedded paclitaxel and chitosan-coated TiO2-embedded paclitaxel nanoparticles. The biomarkers of oxidative-inflammatory status, anti-tumor activities and survival rates of the model were measured.ResultsXRD analysis showed that the peaks of chitosan/TiO2 (anatase) were consistent with those of crystalline TiO2 and broad phase of chitosan. The FTIR spectrum indicated the relevant functional groups in TiO2. Chitosan-coated TiO2-embedded paclitaxel nanoparticles had good biocompatibility and improve antioxidant and anti-inflammatory properties in the osteosarcoma model. Chitosan-coated TiO2-embedded paclitaxel nanoparticles was less toxic to the cells hFob1.19 and more toxic to the cells 143B than TiO2-embedded paclitaxel nanoparticles. Chitosan-coated TiO2-embedded paclitaxel nanoparticles showed significant antitumor activity and increased the survival rate of the osteosarcoma model (P < 0.05).ConclusionsChitosan improved anti-tumor potential of TiO2-embedded paclitaxel nanoparticles in the prevention of osteosarcoma.

Nanoparticle Digestion Simulator Reveals pH-Dependent Aggregation in the Gastrointestinal Tract.

Determining the physicochemical properties of ingested nanoparticles within the gastrointestinal tract (GIT) is critical for evaluating the impact of environmental exposure and potential for nanoparticle drug delivery. However, it is challenging to predict nanoparticle physicochemical properties at the point of intestinal absorption due to the changing chemical environments within the GIT. Herein, a dynamic nanoparticle digestion simulator (NDS) was constructed to examine nanoparticle evolution due to changing pH and salt concentrations in the stomach and upper intestine. This multicompartment, flow-through system simulates digestion by transferring gastrointestinal fluids and digestive secretions at physiologically relevant time scales and flow rates. Pronounced differences in aggregation and aggregate stability were observed with silver nanoparticles (citrate-coated) with an initial hydrodynamic diameter (Dh) of 24.6 ± 0.4 nm examined under fasted (pH 2) and fed (pH 5) gastric conditions using nanoparticle tracking analysis (NTA) for size distributions and transmission electron microscopy with energy dispersive X-ray spectroscopy (TEM-EDX) for morphology and elemental composition. Under fasted stomach conditions, particles aggregated to Dh = 130 ± 10 nm and remained as large aggregates in the upper intestinal compartments (duodenum and jejunum) ending with Dh = 110 ± 20 nm and a smaller mode at 59 ± 8 nm. In contrast, under fed conditions, nanoparticles aggregated to 60 ± 10 nm in the stomach, then disaggregated to individual nanoparticles (26 ± 2 nm) in the intestinal compartments. The NDS provides an analytical approach for studying nanoparticle physicochemical modifications within the GIT and the impacts of intentionally and unintentionally ingested nanoparticles.

Predicting In Vitro Neurotoxicity Induced by Nanoparticles Using Machine Learning.

The practice of non-testing approaches in nanoparticles hazard assessment is necessary to identify and classify potential risks in a cost effective and timely manner. Machine learning techniques have been applied in the field of nanotoxicology with encouraging results. A neurotoxicity classification model for diverse nanoparticles is presented in this study. A data set created from multiple literature sources consisting of nanoparticles physicochemical properties, exposure conditions and in vitro characteristics is compiled to predict cell viability. Pre-processing techniques were applied such as normalization methods and two supervised instance methods, a synthetic minority over-sampling technique to address biased predictions and production of subsamples via bootstrapping. The classification model was developed using random forest and goodness-of-fit with additional robustness and predictability metrics were used to evaluate the performance. Information gain analysis identified the exposure dose and duration, toxicological assay, cell type, and zeta potential as the five most important attributes to predict neurotoxicity in vitro. This is the first tissue-specific machine learning tool for neurotoxicity prediction caused by nanoparticles in in vitro systems. The model performs better than non-tissue specific models.