Uptake Of Nanoparticles Research Articles

PH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases.

Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit®S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.

Uptake of Silver-Containing Nanoparticles in an Estuarine Plant: Speciation and Bioaccumulation.

Understanding the bioaccumulation of silver-containing nanoparticles (Ag-NPs) with different species, concentrations, and sizes in estuarine plants is critical to their related environmental risk. Herein, the distribution of Ag-NPs in tidewater, sediments, and plants (Scirpus triqueter) of field-constructed mesocosm was investigated, where tidewater was exposed to Ag0-NPs and Ag+ at environmentally relevant concentrations. Particle number concentrations (PNCs) and sizes of Ag-NPs with various species were analyzed using a multistep selective dissolution method followed by the single-particle- inductively coupled plasma mass spectrometry technique. After 30 days of exposure, more than half of Ag0-NPs were dissolved to Ag+ and about 1/4 of Ag+ were transformed into Ag0-/AgCl-NPs in tidewater. Ag-NPs in stems exposed to Ag0-NPs were found to be dominated by metallic Ag, while Ag+ exposure led to more Ag2S-NPs in stems. In roots, 71% and 51% of Ag-NPs were found as Ag2S-NPs for Ag0-NPs and Ag+ treatment groups, respectively. Plant stems had a significantly higher enrichment of Ag-NPs than roots. Based on both random forests and structure equation models, it is suggested that salinity of tidewater can regulate Ag0-NPs in tidewater indirectly by influencing AgCl-NPs in tidewater and further affect the total PNCs of Ag-NPs in plant stems. Moreover, elevated sulfate-reducing bacteria (SRB) result in more Ag2S-NPs in rhizosphere sediments, thereby enhancing the bioaccumulation of Ag-NPs by roots.

Bidirectional Uptake, Transfer, and Transport of Dextran-Based Nanoparticles in Plants for Multidimensional Enhancement of Pesticide Utilization.

The development of effective multifunctional nano-delivery approaches for pesticide absorption remains a challenge. Here, a dextran-based pesticide delivery system (MBD) is constructed to deliver tebuconazole for multidimensionally enhancing its effective utilization on tomato plants. Spherical MBD nanoparticles are obtained through two-step esterification of dextran, followed by tebuconazole loading using the Michael addition reaction. Confocal laser scanning microscopy shows that fluorescein isothiocyanate-labeled MBD nanoparticles can be bidirectionally transported in tomato plants and a modified quick, easy, cheap, effective, rugged, and safe-HPLC approach demonstrates the capacity to carry tebuconazole to plant tissues after 24 h of root uptake and foliar spray, respectively. Additionally, MBD nanoparticles could increase the retention of tebuconazole on tomato leaves by up to nearly 2.1 times compared with the tebuconazole technical material by measuring the tebuconazole content retained on the leaves. In vitro antifungal and pot experiments show that MBD nanoparticles improve the inhibitory effect of tebuconazole against botrytis cinerea by 58.4% and the protection against tomato gray molds by 74.9% compared with commercial suspensions. Furthermore, the MBD nanoparticles do not affect the healthy growth of tomato plants. These results underline the potential for the delivery system to provide a strategy for multidimensional enhancement of pesticide efficacy.

Better biocompatibility of nitrogen-doped graphene compared with graphene oxide by reducing cell autophagic flux blockage and cell apoptosis.

Nitrogen-doped graphene (C2 N), a novel graphene-based materials, has been proposed as a potential alternative to graphene oxide (GO) in biomedical applications. However, due to the challenges in synthesizing C2 N, reports in the biomedical field are currently rare. Here, we have modified the reported procedure and successfully synthesized C2 N nanoparticles at 120°C, which we refer to as C2 N-120. The toxicity and biocompatibility of GO and C2 N-120 were evaluated using a mouse model injected with GO/C2 N-120 via the tail vein, as well as cell models treated with GO/C2 N-120. In vivo studies revealed that GO/C2 N-120 showed similar distribution patterns after tail vein injection. The liver, spleen, and lung are the major nanoparticle uptake organs of GO and C2 N-120. However, GO deposition in the major nanoparticle uptake organs was more significant than that of C2 N-120. In addition, GO deposition caused structural abnormalities, increased apoptotic cells, and enhanced macrophage infiltration whereas C2 N-120 exhibited fewer adverse effects. In vitro experiments were conducted using different cell lines treated with GO/C2 N-120. Unlike GO which induced mitochondrial damage, oxidative stress, inflammatory response, autophagic flux blockage and cell apoptosis, C2 N-120 showed lower cytotoxicity in cell models. Our data demonstrated that C2 N-120 exhibits higher biocompatibility than GO, both in vivo and in vitro, suggesting its potential for biomedical application in the future.

Impact of Targeting Moiety Type and Protein Corona Formation on the Uptake of Fn14-Targeted Nanoparticles by Cancer Cells.

The TWEAK receptor, Fn14, is a promising candidate for active targeting of cancer nanotherapeutics to many solid tumor types, including metastatic breast and primary brain cancers. Targeting of therapeutic nanoparticles (NPs) has been accomplished using a range of targeting moieties including monoclonal antibodies and related fragments, peptides, and small molecules. Here, we investigated a full-length Fn14-specific monoclonal antibody, ITEM4, or an ITEM4-Fab fragment as a targeting moiety to guide the development of a clinical formulation. We formulated NPs with varying densities of the targeting moieties while maintaining the decreased nonspecific adhesivity with receptor targeting (DART) characteristics. To model the conditions that NPs experience following intravenous infusion, we investigated the impact of serum exposure in relation to the targeting moiety type and surface density. To further evaluate performance at the cancer cell level, we performed experiments to assess differences in cellular uptake and trafficking in several cancer cell lines using confocal microscopy, imaging flow cytometry, and total internal reflection fluorescence microscopy. We observed that Fn14-targeted NPs exhibit enhanced cellular uptake in Fn14-high compared to Fn14-low cancer cells and that in both cell lines uptake levels were greater than observed with control, nontargeted NPs. We found that serum exposure increased Fn14-targeted NP specificity while simultaneously reducing the total NP uptake. Importantly, serum exposure caused a larger reduction in cancer cell uptake over time when the targeting moiety was an antibody fragment (Fab region of the monoclonal antibody) compared with the full-length monoclonal antibody targeting moiety. Lastly, we uncovered that full monoclonal antibody-targeted NPs enter cancer cells via clathrin-mediated endocytosis and traffic through the endolysosomal pathway. Taken together, these results support a pathway for developing a clinical formulation using a full-length Fn14 monoclonal antibody as the targeting moiety for a DART cancer nanotherapeutic agent.

Simultaneous Electrophysiology and Imaging Reveal Changes in Lipid Membrane Thickness and Tension upon Uptake of Amphiphilic Gold Nanoparticles.

Amphiphilic gold core nanoparticles (AmNPs) striped with hydrophilic 11-mercapto-1-undecanesulfonate (MUS) and hydrophobic 1-octanethiol (OT) ligands are promising candidates for drug carriers that passively and nondisruptively enter cells. Yet, how they interact with cellular membranes is still only partially understood. Herein, we use electrophysiology and imaging to carefully assess changes in droplet interface bilayer lipid membranes (DIBs) incurred by striped AmNPs added via microinjection. We find that AmNPs spontaneously reduce the steady-state specific capacitance and contact angle of phosphatidylcholine DIBs by amounts dependent on the final NP concentration. These reductions, which are greater for NPs with a higher % OT ligands and membranes containing unsaturated lipids but negligible for MUS-only-coated NPs, reveal that AmNPs passively embed in the interior of the bilayer where they increase membrane thickness and lateral tension through disruption of lipid packing. These results demonstrate the enhanced evaluation of nano-bio interactions possible via electrophysiology and imaging of DIBs.

Development and testing of nanoparticles delivery for P7C3 small molecule using injury models.

The use of nanoparticles (NPs) has emerged as a potential tool for safe and effective drug delivery. In the present study, we developed small molecule P7C3-based NPs and tested its efficacy and toxicity along with the tissue specific aptamer-modified P7C3 NPs. The P7C3 NPs were prepared using poly (D, L-lactic-co-glycolic acid) carboxylic acid (PLGA-COOH) polymer, were conjugated with skeletal muscle-specific RNA aptamer (A01B P7C3 NPs) and characterized for its cytotoxicity, cellular uptake, and wound healing in vitro. The A01B P7C3 NPs demonstrated an encapsulation efficiency of 30.2 ± 2.6%, with the particle size 255.9 ± 4.3nm, polydispersity index of 0.335 ± 0.05 and zeta potential of + 10.4 ± 1.8mV. The FTIR spectrum of P7C3 NPs displayed complete encapsulation of the drug in the NPs. The P7C3 NPs and A01B P7C3 NPs displayed sustained drug release in vitro for up to 6 days and qPCR analysis confirmed A01B aptamer binding to P7C3 NPs. The C2C12 cells viability assay displayed no cytotoxic effects of all 3 formulations at 48 and 72h. In addition, the cellular uptake of A01B P7C3 NPs in C2C12 myoblasts demonstrated higher uptake. In vitro assay mimicking wound healing showed improved wound closure with P7C3 NPs. In addition, P7C3 NPs significantly decreased TNF-α induced NF-κB activity in the C2C12/NF-κB reporter cells after 24-hour treatment. The P7C3 NPs showed 3-4-fold higher efficacy compared to P7C3 solutions in both wound-closure and inflammation assays in C2C12 cells. Furthermore, the P7C3 NPs showed 3-4-fold higher efficacy in reducing the infarct size and protected mouse hearts from ex vivo ischemia-reperfusion injury. Overall, this study demonstrates the safe and effective delivery of P7C3 NPs.

Effective translocation of rigid nanoparticles across leaf surfaces by deep eutectic solvents

Nanopesticide delivery systems have great potential for agricultural production. However, rigid nanoparticles have limited absorption and uptake capabilities on the leaf surface owing to the specific structure of the leaf cell. Therefore, in this study, we aimed to design a deep eutectic solvent (DES)–mesoporous silica nanoparticle (MSN) system using maize as a model crop to achieve efficient uptake and translocation of rigid nanoparticles by the leaf surface. In this DES–MSN system, DES modifies the arrangement and spatial structure of lignin and cellulose, thus regulating the function of the leaf barrier and enhancing penetration. Moreover, the DES and MSNs are connected by strong hydrogen bonds, enabling efficient absorption and translocation of rigid nanoparticles on the leaf surface through a “drag” effect. After applying the DES–MSN system on the leaf surface, the distribution and transport characteristics of the pesticide in the plant were considerably altered, as a rapid and enhanced accumulation of pesticides in the roots was achieved. Therefore, our research provides a simple and feasible approach for designing and constructing novel nanopesticides.

Formulation of Thiamine-Laden Chitosan Nanosphere for Nutraceutical Application

Introduction:: Thiamine, often known as vitamin B1, is a water-soluble vitamin that can be added to food or purchased as a supplement. It plays an important role in many cellular processes and is crucial for overall human health. The synthesis and characterization of Thiamineencapsulated chitosan nanospheres for sustained release and improved bioavailability is the major objective of this study. Materials and Methods: The chitosan nanospheres were prepared using sodium tripolyphosphate (TPP) as cross-linking agent. Results:: The ionic interactions between chitosan and TPP produced small-sized stable nanospheres for the incorporation of Thiamine. The conjugate was characterized through a UV spectrophotometer and Fourier Transform Infrared spectroscopy (FTIR). The size and morphology were determined using Zetasizer and Scanning Electron Microscopy (SEM). An average size of 504 nm size was obtained for the nanospheres. The in vitro release studies were performed for 30 days to assess the sustained release of thiamine from nanoencapsulates. Cellular uptake of the thiamine-encapsulated chitosan nanoparticles was studied in the human cervical cancer cell lines (HeLa) and mus-musculus 3T3 L1 cell lines. Conclusion:: This study is an early design and development of a technology for encapsulating water-soluble vitamins in biodegradable polymers, which can be examined for the vitamin's long-term bioavailability.

Theranostic Nanoparticle Uptake in Patient Brain Tumors as Quantified by MP2RAGE T1 Mapping

Modern radiation therapy techniques provide effective treatments for solid tumors, but there remain challenges with delivering high doses to elusive tumors without causing toxicity to surrounding normal tissue. Pre-clinical trials have demonstrated the theranostic properties of a recently developed gadolinium-based nanoparticle (Gd-NP). The first in-human clinical trial was conducted to assess the safety and dose tolerance of intravenous Gd-NPs in combination with whole brain radiotherapy and showed favorable results, including a significant correlation between tumor uptake and therapeutic response. The second, double-blinded, in-human clinical trial is underway in the US and aims to evaluate if brain-directed stereotactic radiation in conjunction with NPs will improve local tumor control compared to radiation alone. The current work investigates uptake patterns in brain tumors of 23 patients as quantified by magnetization prepared 2 rapid gradient echo (MP2RAGE) T1 mapping. A phantom containing eight vials of NP-saline solutions at varying concentrations was created to examine the relationship between NP concentration and longitudinal relaxation (T1, in seconds). This relationship is known as relaxivity and is dependent on the contrast agent, field strength and T1 mapping sequence. A 3T MAGNETOM Vida scanner and MP2RAGE sequence were used to image the phantom and MP2RAGE T1 maps were calculated using Bloch equations (QMRLab software). Relaxivity was determined and applied to 23 patient T1 maps (pre- and post- Gd-NP administration) to calculate uptake on an individual tumor basis. Theranostic NP uptake was calculated for every voxel in each of 129 brain metastases and examined for patterns in quantity and distribution. Average individual tumor uptake ranged from 0.02-0.12 mg/ml, where average overall uptake was equal to 0.05 mg/ml. A relationship between tumor diameter and mean NP concentration was observed and best represented by a power-based curve (R2 = 0.92). In contrast, patients with suspected placebo administration appeared to have no uptake and therefore no relationship with tumor diameter. The distribution of NP concentration within the tumor was also examined; on average, linear uptake profiles through tumor centroids (ant-post, left-right) demonstrated roughly gaussian patterns of uptake with lower concentrations at the tumor edges and higher concentrations at the tumor center. This pattern indicates robust tumor penetration and may have implications for amplifying radiation dose to hypoxic tumors. Gd-NP uptake in brain metastases can be quantified using MP2RAGE T1 mapping. Uptake was determined for each voxel in each tumor volume, where a gaussian pattern of spatial concentrations was observed. This analysis procedure will be applied to the full data set, when available, to evaluate the impact of NP uptake (in conjunction with radiation therapy) within individual patients and individual tumors.

Direct Uptake and Intracellular Dissolution of HgS Nanoparticles: Evidence from a Bacterial Biosensor Approach.

Mercury sulfide nanoparticles (HgSNPs), which occur widely in oxic and anoxic environments, can be microbially converted to highly toxic methylmercury or volatile elemental mercury, but it remains challenging to assess their bioavailability. In this study, an Escherichia coli-based whole-cell fluorescent biosensor was developed to explore the bioavailability and microbial activation process of HgSNPs. Results show that HgSNPs (3.17 ± 0.96 nm) trigger a sharp increase in fluorescence intensity of the biosensor, with signal responses almost equal to that of ionic Hg (Hg(II)) within 10 h, indicating high bioavailability of HgSNP. The intracellular total Hg (THg) of cells exposed to HgSNPs (200 μg L-1) was 3.52-8.59-folds higher than that of cells exposed to Hg(II) (200 μg L-1), suggesting that intracellular HgSNPs were only partially dissolved. Speciation analysis using size-exclusion chromatography (SEC)-inductively coupled plasma mass spectrometry (ICP-MS) revealed that the bacterial filtrate was not responsible for HgSNP dissolution, suggesting that HgSNPs entered cells in nanoparticle form. Combined with fluorescence intensity and intracellular THg analysis, the intracellular HgSNP dissolution ratio was estimated at 22-29%. Overall, our findings highlight the rapid internalization and high intracellular dissolution ratio of HgSNPs by E. coli, and intracellular THg combined with biosensors could provide innovative tools to explore the microbial uptake and dissolution of HgSNPs.

Foliar-applied nano-cerium dioxide differentially affect morpho-physiological traits and essential oil profile of Salvia mirzayanii Rech. f. & Esfand under drought stress and post-stress recovery conditions

Drought stress is known to diminish the growth and yield of plants by altering the physiological, biochemical and molecular processes, thus threatening food security worldwide. Nanoparticles (NPs) have emerged as an effective strategy to raise plant productivity under current rapid environmental challenges. However, there is little literature on mechanisms underlying the beneficial role of re-watering in drought-stressed plants treated with NPs. In this study, the effects of cerium dioxide nanoparticles [(CeO2 NPs), 0 (control), 125, 250, 500, and 1000 mL L−1] were investigated on morpho-physiological and phytochemical traits of Salvia mirzayanii plants under different drought stress intensities [(25%, 50%, 75%, and 100% (control) of field capacity (FC) moisture] and post-stress re-watering (recovery) in a three-way factorial arrangement based on randomized complete block design. Uptake and accumulation of CeO2 NPs in the leaf tissue of plant samples were confirmed using SEM and EDX techniques. The results of ANOVA demonstrated that growth and physio-phytochemical traits were significantly (p < 0.05) affected by individual treatment and/or their double and triple interactions. Exposure to various levels of CeO2 NPs during drought stress mitigated the adverse effects of stress on growth parameters (e.g., plant height, shoot and root dry weights, and root length) and photosynthetic pigments (chlorophyll a and b) content compared to the respective controls in varying degrees. However, proline and essential oil content were increased in drought-stressed plants, and tended to decrease during the period of recovery. Before re-watering, the antioxidant enzymes, CAT, POD, and SOD, activity in leaf tissues was increased with the increase of drought stress intensity upon both treated and non-treated CeO2 NPs conditions. However, the three-way interaction results demonstrated that recovery after drought stress following CeO2 NPs application particularly 1000 mL L−1 decreased the activity of antioxidant enzymes compared to the controls. Based on GC and GC-MS analysis, all essential oil samples predominantly composed of oxygenated monoterpenes and sesquiterpenes including Decane, Spathulenol, Octane, α-Terpinyl acetate, Hexyl isovalerate, Dodecane, Butanoic acid, Linalool, δ-Cadinene, Muurolol, α-Cadinol, Eudesm-7(11)-en-4-ol, which significantly (p < 0.05) changed under different experimental treatments. The recovery after stress, however, increased only the content of δ-Cadinene in plants from severe drought stress upon foliar application of 1000 mL L−1 CeO2 NPs compared to the non-recovery period. Conclusively, integrative use of CeO2 NPs and re-watering after drought stress could be an encouraging and eco-friendly strategy to improve both drought tolerance, growth and pyhtochemical contents in S. mirzayanii plants.

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger receptor MARCO in mice, non-human primates and humans. Therapeutic blockade of MARCO is shown to decrease the phagocytic uptake of nanoparticles and improve the antitumour effect of clinically approved cancer nanotherapeutics in young but not aged mice. Together, these results reveal an age-associated disparity in the phagocytic clearance of nanotherapeutics that affects their antitumour response, thus providing a strong rationale for an age-appropriate approach to cancer nanomedicine.

The uptake, elimination, and toxicity of silver nanoparticles and silver ions in single-species and natural mixed-species bacterial biofilms

In nature, microorganisms predominantly exist as biofilms, which can reduce the bioavailability of toxic metals in water by adsorbing them. In this study, we investigated the adsorption, elimination, and toxicity of silver nanoparticles (AgNPs) and silver nitrate (AgNO3) in biofilms of the model bacterium Escherichia coli and those composed of natural mixed-species (NMS). Biofilms were exposed to different metal concentrations for 72 h, after which, they were transferred to a clean medium for 7 days to study the elimination of AgNPs and Ag+. We found that pseudo-second order kinetics predominated, and adsorption was jointly governed by external mass transfer and intraparticle diffusion. NMS biofilms were much more tolerant to AgNPs and Ag+ than E. coli biofilms, and Ag+ was much more toxic to both the biofilms than AgNPs. The concentrations of proteins, polysaccharides, and internal metabolites like respiratory chain dehydrogenase and cyclic diguanosine monophosphate were 0.3 to 3.7 fold greater in NMS biofilms than in E. coli biofilms, while those of reactive oxygen species and lactate dehydrogenase were 0.6 to 1.1 fold lower in NMS biofilms, highlighting a significant advantage that metal-exposed NMS biofilms enjoy in terms of both structure and metabolic function. These findings improve our understanding of the potential environmental risks of engineered nanoparticles and provide new insights into the bioremediation of nanoparticles-contaminated aquatic environments using biofilms.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

Nanoparticles at the maternal-fetal interface

The increasing production of intentional and unintentional nanoparticles (NPs) has led to their accumulation in the environment as air and ground pollution. The heterogeneity of these particles primarily relies on the NP physicochemical properties (i.e., chemical composition, size, shape, surface chemistry, etc.). Pregnancy represents a vulnerable life stage for both the woman and the developing fetus. The ubiquitous nature of these NPs creates a concern for developmental fetal exposures. At the maternal-fetal interface lies the placenta, a temporary endocrine organ that facilitates nutrient and waste exchange as well as communication between maternal and fetal tissues. Recent evidence in human and animal models identifies that gestational exposure to NPs results in placental translocation leading to local effects and endocrine disruption. Currently, the mechanisms underlying placental translocation and cellular uptake of NPs in the placenta are poorly understood. The purpose of this review is to assess the current understanding of the physiochemical factors influencing NP translocation, cellular uptake, and endocrine disruption at the maternal-fetal interface within the available literature.

Exploring the impact of severity in hepatic fibrosis disease on the intrahepatic distribution of novel biodegradable nanoparticles targeted towards different disease biomarkers

Nanoparticle-based drug delivery systems (DDS) have shown promising results in reversing hepatic fibrosis, a common pathological basis of chronic liver diseases (CLDs), in preclinical animal models. However, none of these nanoparticle formulations has transitioned to clinical usage and there are currently no FDA-approved drugs available for liver fibrosis. This highlights the need for a better understanding of the challenges faced by nanoparticles in this complex disease setting. Here, we have systematically studied the impact of targeting strategy, the degree of macrophage infiltration during fibrosis, and the severity of fibrosis, on the liver uptake and intrahepatic distribution of nanocarriers. When tested in mice with advanced liver fibrosis, we demonstrated that the targeting ligand density plays a significant role in determining the uptake and retention of the nanoparticles in the fibrotic liver whilst the type of targeting ligand modulates the trafficking of these nanoparticles into the cell population of interest - activated hepatic stellate cells (aHSCs). Engineering the targeting strategy indeed reduced the uptake of nanoparticles in typical mononuclear phagocyte (MPS) cell populations, but not the infiltrated macrophages. Meanwhile, additional functionalization may be required to enhance the efficacy of DDS in end-stage fibrosis/cirrhosis compared to early stages.

Rapid Internalization of Nanoparticles by Human Cells at the Single Particle Level.

Nanoparticle uptake by cells has been studied for applications both in nanomedicine and in nanosafety. While the majority of studies have focused on the biological mechanisms underlying particle internalization, less attention has been given to questions of a more quantitative nature, such as how many nanoparticles enter cells and how rapidly they do so. To address this, we exposed human embryonic kidney cells to 40-200 nm carboxylated polystyrene nanoparticles and the particles were observed by live-cell confocal and super-resolution stimulated emission depletion fluorescence microscopy. How long a particle remained at the cell membrane after adsorbing onto it was monitored, distinguishing whether the particle ultimately desorbed again or was internalized by the cell. We found that the majority of particles desorb, but interestingly, most of the particles that are internalized do so within seconds, independently of particle size. As this is faster than typical endocytic mechanisms, we interpret this observation as the particles entering via an endocytic event that is already taking place (as opposed to directly triggering their own uptake) or possibly via an as yet uncharacterized endocytic route. Aside from the rapidly internalizing particles, a minority of particles remain at the membrane for tens of seconds to minutes before desorbing or being internalized. We also followed particles after cell internalization, observing particles that appeared to exit the cell, sometimes as rapidly as within tens of seconds. Overall, our results provide quantitative information about nanoparticle cell internalization times and early trafficking.

The development of folate-functionalised palladium nanoparticles for folate receptor targeting in breast cancer cells.

Folate receptor-targeted therapy has excellent prospects for the treatment of breast cancer. A non-toxic concentration of folate-conjugated palladium-based nanoparticles was used to target the overexpressed folate receptor on breast cancer cells. The folate-conjugated nanoparticles were tailored to accumulate selectively in cancer cells relative to normal cells via the folate receptor. The MDA-MB-231, MDA-MB-468, MCF-7 breast cancer cell lines, and MCF-10A normal cell lines were used in the study. Qualitative and quantitative analysis of nanoparticle cellular uptake and accumulation was conducted using transmission electron microscopy and inductively coupled plasma-optical emission spectroscopy. The findings proved that folate-conjugated palladium nanoparticles successfully and preferentially accumulated in breast cancer cells. We conclude that folate-conjugated palladium nanoparticles can be potentially used to target breast cancer cells for radiopharmaceutical applications.

Substrate Stiffness and Particle Properties Influence Cellular Uptake of Nanoparticles and Viruses from the Ventral Side

AbstractIt is a long‐standing challenge to exploit cellular uptake mechanisms to deliver desired cargo into cells, for example, specific drugs or gene editing techniques. This study introduces a bioinspired material approach where nanoparticles are presented at the ventral side of cells adhering to engineered extracellular matrices. The effect of matrix stiffness on cell adhesion and mechanics, as well as on particle internalization by clathrin‐mediated endocytosis (CME), is investigated for varying particle size and surface functionalization. The results presented here show that substrate stiffness affects both cell adhesion and particle internalization, with softer substrates promoting higher levels of particle uptake. However, the activation of the CME pathway, either mechanically by particle size or functionally by receptor binding, regulates the sensitivity of cellular particle uptake to matrix stiffness. Finally, adeno‐associated viruses as the leading platform for therapeutic gene delivery are used as model cargo to showcase the importance of considering multiple components when designing delivery systems. These findings indicate that particle uptake is a multifaceted process that can be improved by the appropriate combination of extracellular environment mechanics and cargo properties.