Uptake Of Nanoparticles Research Articles

Polyelectrolyte Brush Interacting with Ampholytic Nanoparticles as Coarse-Grained Models of Globular Proteins: Poisson-Boltzmann Theory.

The self-consistent field Poisson-Boltzmann framework is applied to analyze equilibrium partitioning of ampholytic nanoparticles (NPs) between buffer solution and polyelectrolyte (PE) polyanionic brush. We demonstrate that depending on pH and salt concentration in the buffer solution, interactions between ionizable (acidic and basic) groups on the NP surface and electrostatic field created by PE brush may either lead to the spontaneous uptake of NPs or create an electrostatic potential barrier, preventing the penetration of NPs inside PE brush. The capability of PE brush to absorb or repel NPs is determined by the shape of the insertion free energy that is calculated as a function of NP distance from the grafting surface. It is demonstrated that, at a pH value below or slightly above the isoelectric point (IEP), the electrostatic free energy of the particle is negative inside the brush and absorption is thermodynamically favorable. In the latter case, the insertion free energy exhibits a local maximum (potential barrier) at the entrance to the brush. An increase in pH leads to the shallowing of the free energy minimum inside the brush and a concomitant increase in the free energy maximum, which may result in kinetic hindering of NP uptake. Upon further increase in pH the insertion free energy becomes positive, making NP absorption thermodynamically unfavorable. An increase in salt concentration diminishes the depth of the free energy minimum inside the brush and eventually leads to its disappearance. Hence, in accordance with existing experimental data our theory predicts that an increase in salt concentration suppresses absorption of NPs (protein globules) by PE brush in the vicinity of IEP. The interplay between electrostatic driving force for NP absorption and osmotic repelling force (proportional to NP volume) indicates that for large NPs with relatively small number of ionizable groups osmotic repulsion overcomes electrostatic attraction preventing thereby absorption of NPs by PE brush.

Erythrocyte−cancer hybrid membrane-coated reduction-sensitive nanoparticles for enhancing chemotherapy efficacy in breast cancer

Cell-membrane-coated biomimetic nanoparticles (NPs) have attracted great attention due to their prolonged circulation time, immune escape mechanisms and homotypic targeting properties. Biomimetic nanosystems from different types of cell -membranes (CMs) can perform increasingly complex tasks in dynamic biological environments thanks to specific proteins and other properties inherited from the source cells. Herein, we coated doxorubicin (DOX)-loaded reduction-sensitive chitosan (CS) NPs with 4T1 cancer cell -membranes (CCMs), red blood cell -membranes (RBCMs) and hybrid erythrocyte-cancer membranes (RBC-4T1CMs) to enhance the delivery of DOX to breast cancer cells. The physicochemical properties (size, zeta potential and morphology) of the resulting RBC@DOX/CS-NPs, 4T1@DOX/CS-NPs and RBC-4T1@DOX/CS-NPs, as well as their cytotoxic effect and cellular NP uptake in vitro were thoroughly characterized. The anti-cancer therapeutic efficacy of the NPs was evaluated using the orthotopic 4T1 breast cancer model in vivo. The experimental results showed that DOX/CS-NPs had a DOX-loading capacity of 71.76 ± 0.87 %, and that coating of DOX/CS-NPs with 4T1CM significantly increased the NP uptake and cytotoxic effect in breast cancer cells. Interestingly, by optimizing the ratio of RBCMs:4T1CMs, it was possible to increase the homotypic targeting properties towards breast cancer cells. Moreover, in vivo tumor studies showed that compared to control DOX/CS-NPs and free DOX, both 4T1@DOX/CS-NPs and RBC@DOX/CS-NPs significantly inhibited tumor growth and metastasis. However, the effect of 4T1@DOX/CS-NPs was more prominent. Moreover, CM-coating reduced the uptake of NPs by macrophages and led to rapid clearance from the liver and lungs in vivo, compared to control NPs. Our results suggest that specific self-recognition to source cells resulting in homotypic targeting increased the uptake and the cytotoxic capacity of 4T1@DOX/CS-NPs by breast cancer cells in vitro and in vivo. In conclusion, tumor-disguised CM-coated DOX/CS-NPs exhibited tumor homotypic targeting and anti-cancer properties, and were superior over targeting with RBC-CM or RBC-4T1 hybrid membranes, suggesting that the presence of 4T1-CM is critical for treatment outcome.

Self-Assembled Monolayers Derived from Positively Charged Adsorbates on Plasmonic Substrates for MicroRNA Delivery: A Review

MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems such as liposomes and nanoparticles. We also examine the use of nanoparticles for miRNA-based diagnostics. We focus specifically on non-viral delivery systems utilizing coinage metals in the form of nanoparticles and the use of self-assembled monolayers (SAMs) as a method of surface modification. We review the use of SAMs for the conjugation and delivery of small noncoding ribonucleic acid (ncRNA), particularly SAMs derived from positively charged adsorbates to generate charged surfaces that can interact electrostatically with negatively charged miRNA. We also discuss the effects of the cellular uptake of gold and other plasmonic nanoparticles, as well as the challenges associated with the degradation of oligonucleotides. Our review highlights the potential of SAM-based systems as versatile and robust tools for delivering miRNA and other RNAs in vitro and in vivo and the need for further research to address the challenges associated with miRNA delivery and diagnostics.

Alterations induced by titanium dioxide nanoparticles (nano-TiO2) in fertilization and embryonic and larval development of the tropical sea urchin Lytechinus variegatus

The release of nanomaterials into the environment is the cause of an emerging concern. Titanium dioxide nanoparticles (nano-TiO2) among the most produced nanomaterials, has been documented in marine coastal areas posing a threat on marine biota. Sea urchin embryos are recognized as suitable bioindicators in ecological risk assessment and recently for nanomaterials. This study investigated the impact of nano-TiO2 on fertilization, embryonic and larval development of the tropical sea urchin Lytechinus variegatus in a range of concentrations (0.005–5 μg/mL) which includes environmentally relevant ones. The behavior of nano-TiO2 in tropical natural seawater was determined by dynamic light scattering (DLS) and toxicity was evaluated through fertilization and embryotoxicity tests, and morphological/morphometric analyses of sea urchin's larvae. Limited toxicity was recorded for nano-TiO2 in tropical sea urchin embryos and larvae, except for effects at the gastrula stage at 0.005 μg/mL. Large agglomerates of nano-TiO2 (5 μg/mL) were observed adhering onto sea urchin larvae thus probably preventing nanoparticles uptake at the highest concentrations (>0.005 μg/mL). Environmental levels of nano-TiO2 are able to cause toxicity on tropical sea urchin L. variegatus embryos with potential consequences on populations and their ecological role in tropical coastal areas.

Mannosylated preactivated hyaluronic acid-based nanostructures for bacterial infection treatment

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of −15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.

Encapsulation of Pioglitazone into Polymer-Nanoparticles for Potential Treatment of Atherosclerotic Diseases.

Atherosclerosis is one of the most urgent global health subjects, causes millions of deaths worldwide, and is associated with enormous healthcare costs. Macrophages are the root cause for inflammatory onset and progression of the disease but are not addressed by conventional therapy. Therefore, we used pioglitazone, which is a drug initially used for diabetes therapies, but at the same time has great potential regarding the mitigation of inflammation. As yet, this potential of pioglitazone cannot be exploited, as drug concentrations at the target site in vivo are not sufficient. To overcome this shortcoming, we established PEG-PLA/PLGA-based nanoparticles loaded with pioglitazone and tested them in vitro. Encapsulation of the drug was analyzed by HPLC and revealed an outstanding encapsulation efficiency of 59% into the nanoparticles, which were 85 nm in size and had a PDI of 0.17. Further, uptake of our loaded nanoparticles in THP-1 macrophages was comparable to the uptake of unloaded nanoparticles. On the mRNA level, pioglitazone-loaded nanoparticles were superior to the free drug by 32% in increasing the expression of the targeted receptor PPAR-γ. Thereby the inflammatory response in macrophages was ameliorated. In this study, we take the first step toward an anti-inflammatory, causal antiatherosclerotic therapy, using the potential of the already established drug pioglitazone, and enable it to enrich at the target site by using nanoparticles. An additional crucial feature of our nanoparticle platform is the versatile modifiability of ligands and ligand density, to achieve an optimal active targeting effect in the future.

Non-specific uptake of magnetic iron oxide nanoparticles by Adrenocortical carcinoma and Endothelial cells

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Uptake, accumulation, toxicity, and interaction of metallic-based nanoparticles with plants: current challenges and future perspectives.

The rapid development of industrialization is causing several fundamental problems in plants due to the interaction between plants and soil contaminated with metallic nanoparticles (NPs). Numerous investigations have been conducted to address the severe toxic effects caused by nanoparticles in the past few decades. Based on the composition, size, concentration, physical and chemical characteristics of metallic NPs, and plant types, it enhances or lessens the plant growth at various developmental stages. Metallic NPs are uptaken by plant roots and translocated toward shoots via vascular system based on composition, size, shape as well as plant anatomy and cause austere phytotoxicity. Herein, we tried to summarize the toxicity induced by the uptake and accumulation of NPs in plants and also we explored the detoxification mechanism of metallic NPs adopted by plants via using different phytohormones, signaling molecules, and phytochelatins. This study was intended tobe an unambiguous assessment including current knowledge on NPs uptake, accumulation, and translocation in higher plants. Furthermore, it will also provide sufficient knowledge to the scientific community to understand the metallic NPs-induced inhibitory effects and mechanisms involved within plants.

A Carrier-Free Nanomedicine Enables Apoptosis-Ferroptosis Synergistic Breast Cancer Therapy by Targeting Subcellular Organelles.

The heterogeneity of cancer cells disables the single-cell death patterns in subtypes of cells with different genotypes and phenotypes, such as refractory triple-negative breast cancer (TNBC). Therefore, the combination of multiple death modes, such as the proven cooperative apoptosis and ferroptosis, is expected to sensitize in treating TNBC. Herein, carrier-free theranostic ASP nanoparticles (NPs) were designed for wiping out TNBC by synergistic apoptosis and ferroptosis, which was self-assembled by aurantiamide acetate (Aa), scutebarbatine A (SA), and palmitin (P). Structurally, the rigid parent nucleus of SA and hydrophobic chain of P combined with the Aa to form an ordered nanostructure by noncovalent bonding forces. This self-assembly example applies to the design of nanomedicines based on more than two natural products. Notably, enhanced permeability and retention (EPR) effects and mitochondrial-lysosomal targeting empower ASP NPs to pinpoint tumor sites. Especially, Aa and P induced mitochondrial apoptosis of cancer cells, while SA and P inhibited TNBC by ferroptosis and upregulating p53. More interestingly, the combination of Aa, SA, and P enhanced the uptake of ASP NPs by cancer cell membranes. Overall, the three compounds synergize with each other to exert excellent anticancer effects.

Label-Free Tracking of Nanoprodrug Cellular Uptake and Metabolism Using Raman and Autofluorescence Imaging.

Nano-DDS, a drug delivery system using nanoparticles, is a promising tool to reduce adverse drug reactions and maximize drug efficiency. Understanding the intracellular dynamics following the accumulation of nanoparticles in tissues, such as cellular uptake, distribution, metabolism, and pharmacological effects, is essential to maximize drug efficiency; however, it remains elusive. In this study, we tracked the intracellular behavior of nanoparticles of a prodrug, cholesterol-linked SN-38 (CLS), in a label-free manner using Raman and autofluorescence imaging. Bright autofluorescent spots were observed in cells treated with CLS nanoparticles, and the color tone of the bright spots changed with incubation time. The Raman spectra of the bright spots showed that the autofluorescence came from the nanoparticles taken into cells, and the change in color of bright spots indicated that CLS turned into SN-38 via hydrolysis inside a cell. It was found that most of the SN-38 were localized in small regions in the cytoplasm even after the conversion from CLS, and only a small amount of SN-38 was dissolved and migrated into other cytoplasm regions and the nucleus. The massive size growth of cells was observed within several tens of hours after the treatment with CLS nanoparticles. Moreover, Raman images of cells using the cytochrome c band and the fluorescence images of cells stained with JC-1 showed that cellular uptake of CLS nanoparticles efficiently caused mitochondrial damage. These results show that the combination of Raman and autofluorescence imaging can provide insight into the intracellular behavior of prodrug nanoparticles and the cell response and facilitate the development of nano-DDSs.

Polystyrene Nanoparticle Uptake and Deposition in Silkworm and Influence on Growth

This work reports the biological toxicity of nano plastic particles (NPs) to silkworms fed on the bait dopped with polystyrene encapsulated luminescent nanoparticles. The processes of NPs intake and excretion were monitored by means of time-gated optical imaging (TGI) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS), which allowed the quantification of the spatiotemporal deposition of NPs in an individual silkworm. The rates of NPs excretion and sequestration were found to be 99.92% and 0.08%, respectively, and the NPs retentate stayed mainly in the fat body (67.7%), digestive tract (18.0%), and head (7.54%). Adverse effects of NPs exposure were accordingly confirmed such as growth retardation and smaller physique. The results of the present work confirmed the possibility of nano-plastics accumulating and transmitting along the food chain in terrestrial ecosystems. The present work demonstrates the potential of employing silkworm as a model of full metamorphosed insects for exploring the biological impact of NPs on congeneric terrestrial animals, as well as the efficacy of the TGI-MS modality for in situ visualizing and quantifying the propagation of NPs via the primary food chain.

Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery

Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic-co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf® lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 ± 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simulated lung fluid), and demonstrated cytocompatibility up to 1000 μg/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alveolar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.

Quantifying Intracellular Nanoparticle Distributions with Three-Dimensional Super-Resolution Microscopy.

Super-resolution microscopy can transform our understanding of nanoparticle-cell interactions. Here, we established a super-resolution imaging technology to visualize nanoparticle distributions inside mammalian cells. The cells were exposed to metallic nanoparticles and then embedded within different swellable hydrogels to enable quantitative three-dimensional (3D) imaging approaching electron-microscopy-like resolution using a standard light microscope. By exploiting the nanoparticles' light scattering properties, we demonstrated quantitative label-free imaging of intracellular nanoparticles with ultrastructural context. We confirmed the compatibility of two expansion microscopy protocols, protein retention and pan-expansion microscopy, with nanoparticle uptake studies. We validated relative differences between nanoparticle cellular accumulation for various surface modifications using mass spectrometry and determined the intracellular nanoparticle spatial distribution in 3D for entire single cells. This super-resolution imaging platform technology may be broadly used to understand the nanoparticle intracellular fate in fundamental and applied studies to potentially inform the engineering of safer and more effective nanomedicines.

Size-dependent cellular uptake of sodium alginate passivated tin dioxide nanoparticles in triple-negative breast cancer cells

The new development of inorganic (IO) nanoparticle (NPs)-based nanomedicines in anticancer therapy is an active area of research. The cellular uptake of IO NPs plays a crucial role in their efficacy as anticancer agents. In this case, IO NPs cellular uptake depends on physical and chemical parameters, including size, shape, and surface modification of the nanoparticles. From the cellular uptake, one of the essential parameters for small size plays a critical role in the NPs' due to their ability to passively diffuse across the cell membrane or enter cells through endocytosis. In this study, the inorganic SnO2 (tin dioxide) and SA (sodium alginate) were made into SnO2 (SASnO2) using a simple one-pot green method. Biomedical studies have shown that SASnO2 NPs exhibit greater antibacterial, antioxidant, and anticancer properties than SnO2 NPs. The prepared SnO2 and SASnO2 NPs were tested against breast cancer cells in anticancer studies. In cellular uptake studies, the smaller size of SASnO2 NPs (19 nm) resulted in higher cellular uptake compared to SnO2 NPs (38 nm). The larger surface area of these SASnO2 NPs allows for more contact with biological membranes and internalization (cell uptake) by cancer cells, resulting in enhanced anticancer therapy when using SASnO2 NPs.

Abstract 835: Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers

Abstract Sixty percent of melanoma patients present brain metastases, having low response rates to current systemic therapies, which do not prolong survival. New therapeutic options to address this clinical need are urgent. Here, we report the development of a polymeric nanoparticle as a cancer nanovaccine capable of selectively co-targeting toll-like receptor function and PD-L1 expression to improve antigen presentation and subsequent effector immune cell function within brain microenvironment. Mannose-poly(lactic-co-glycolic acid)/poly(lactic acid) (man-PLGA/PLA) nanoparticles (NP) were prepared by a modified double emulsion solvent evaporation method, to deliver combinations of melanoma neoantigens, toll-like receptor ligands and regulators of the PD-1/PD-L1 axis. NP physicochemical properties were fully characterized, including size, surface charge and morphology. The amount of melanoma neoantigens and immune regulators entrapped within NP was determined by HPLC. Immature dendritic cells (DC) were used to evaluate the impact of NP on cell viability, and to assess NP uptake kinetics by flow cytometry. NP ability to target and trigger the activation of DC and T cells, was assessed in the lymph nodes and spleen of immunized mice. The NP anti-tumor immune-mediated effect was evaluated in vivo in two primary melanoma-bearing immunocompetent mouse models (B16F10 and B16MO5), and in a melanoma brain metastasis (MBM) mouse model (B16F10), which also included the immune profiling within tumor site by flow cytometry, before and after treatment.NP presented an average diameter of 180 nm, narrow polydispersity index, surface charge close to neutrality, spherical morphology, and high loadings of the neoantigens and immunoregulators. NP did not affect DC viability and were extensively internalized by immature DC. NP were preferentially taken-up in vivo by DC, increasing the expression of activation/maturation markers at DC surface, such as CD80 and CD86. NP elicited antigen-specific T-cell responses, by the significant increase in the expression of TNF-alpha and IFN-gamma (TH1-guided response). In vivo combination of NP with anti-PD-L1 induced a potent immune-mediated anti-tumor response in both primary and preclinical models of MBM, overcoming tumor development with an increased overall survival. This combination re-shaped immune and stroma cell populations in primary tumor and MBM microenvironment, which presented a marked infiltration of cytotoxic T cells that correlated with a decreased expression of PD-1 and PD-L1 within the TME. The synergy between our nanovaccine and anti-PD-L1 provide essential insights to devise alternative combinations regiments to improve the efficacy of immune checkpoint inhibitors in metastatic melanoma, thus opening new line for this unmet medical need. Citation Format: Barbara Carreira, Rita A. Acúrcio, Sabina Pozzi, Ron Kleiner, Liane I. Moura, Ana I. Matos, Daniela vaskovich, Carina Peres, Adelaide Fernandes, Sara Xapelli, Ronit Satchi-Fainaro, Helena F. Florindo. Translational nanotechnology-based cancer vaccine to re-educate host immune response against metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 835.

Foliar applied titanium dioxide nanoparticles (TiO2 NPs) modulate growth, physiological and phytochemical traits in Melissa officinalis L. under various light intensities

Lemon balm (Melissa officinalis L.) is a valuable medicinal plant belonging to the mint family Lamiaceae with different uses in the food, cosmetic-hygienic, and pharmaceutical industries. Therefore, it is crucial to identify novel factors affecting growth, yield, and phytochemical compounds of this plant. In the current study, titanium dioxide (TiO2) nanoparticles (NPs) were foliarly applied at different concentrations (0, 50, and 100 mg L−1) following various light intensities (full (control), 75% and 50% sunlight) on lemon balm in a factorial experiment based on randomized complete block design (RCBD) with three replications (n = 3) for two continues years. IAnalytical techniques, SEM and EDX analyses, confirmed the uptake of TiO2 NPs through aerial parts of plant. Output of shoot dry weight, chlorophyll a (Chl-a) content, and total Chl and relative water content (RWC) were at their highest levels on plants grown at 50% light intensity upon foliar application of TiO2 NPs (100 mg L−1) in both years. High shading (50% of light intensity) without TiO2 NPs application markedly reduced EO content (by 60%), when compared to full solar radiation and exposure to TiO2 NPs (at 50 and 100 mg L−1) during two experimental years. Neral and geranial were the two main components of EO, with 30.7% and 45.05% in the first year of experiment, followed by 30.24% and 43.03% in full light intensity under 100 mg L−1 TiO2 NPs applications in the second year, respectively. Thus, a relatively shady environment and 100 mg L−1 TiO2 NPs foliar spray are recommended to attain a higher yield in lemon balm plants. Key findings of this study revealed the beneficial effects of high light intensity with TiO2 NPs foliar spray to improve the quality and quantity output of EO rich in neral and geranial constituents.

Ryngo 1-23 Enhances the Uptake of Polymer-Encapsulated Nanoparticles by Nonphagocytic Cells

Ryngo 1-23 Enhances the Uptake of Polymer-Encapsulated Nanoparticles by Nonphagocytic Cells

Uptake of TiO2 Nanoparticles was Linked to Variation in net Cation flux in Wheat Seedlings

Titanium dioxide nanoparticles (TiO2 NPs) are ubiquitous in the environment and enter the terrestrial food chain via plant uptake. However, plant uptake behaviors of TiO2 NPs remain elusive. Here, the uptake kinetics of TiO2 NPs by wheat (Triticum aestivum L.) seedlings and the effects on cation flux in roots were examined in a hydroponic system. Uptake rate of TiO2 NPs ranged from 119.0 to 604.2mg kg- 1h- 1 within 8h exposure. NP uptake decreased by 83% and 47%, respectively, in the presence of sodium azide (NaN3) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), indicating an energy-dependent uptake of TiO2 NPs. Moreover, accompanied with TiO2 NP uptake, net influx of Cd2+ decreased by 81%, while Na+ flux shifted from inflow to outflow at the meristematic zone of root. These findings provide valuable information for understanding plant uptake of TiO2 NPs.

Can histamine cause an enhancement of the cellular uptake and cytotoxicity of doxorubicin-loaded polylactide nanoparticles?

Histamine (His) in humans is physiologically involved in neurotransmission and increases vascular permeability during the development of inflammatory response and immunity. It could be used to enhance drug-loaded nanoparticles (NPs) distribution. However, it cannot be freely delivered due to the risk of His-dose-dependent deleterious effects. His can be attached to the polymeric backbone during polymerization to overcome this limitation. In this study, His was used as an initiator of lactide polymerization, and the obtained macromolecules were subsequently used to prepare doxorubicin (DOX)-loaded NPs by nanoprecipitation and microfluidics for examination of anti-cancer properties. Notably, the in vitro activity towards gastric cancer cells (AGS) of the NPs composed of histamine-functionalized polylactides (PLAs) was greatly enhanced compared to control NPs built from hydroxy‑functionalized PLAs. Furthermore, Zonula occludens-1 (ZO-1) tight junction protein production was significantly diminished after treating cells with DOX-loaded NPs assembled with PLAs with histamine residues. These results demonstrate the synergistic effect in cytotoxicity towards gastric cancer cells of DOX and the histamine that are carried by NPs. It is believed that His-DOX NPs strategy may lead to effective, targeted, and low-toxic delivery of drugs into cancer cells.