Entry Of Nanoparticles Research Articles

Uptake, Translocation, Toxicity, and Impact of Nanoparticles on Plant Physiological Processes

The application of nanotechnology in agriculture has increased rapidly. However, the fate and effects of various nanoparticles on the soil, plants, and humans are not fully understood. Reports indicate that nanoparticles exhibit positive and negative impacts on biota due to their size, surface property, concentration within the system, and species or cell type under test. In plants, nanoparticles are translocated either by apoplast or symplast pathway or both. Also, it is not clear whether the nanoparticles entering the plant system remain as nanoparticles or are biotransformed into ionic forms or other organic compounds. Controversial results on the toxicity effects of nanomaterials on the plant system are available. In general, the nanomaterial toxicity was exerted by producing reactive oxygen species, leading to damage or denaturation of various biomolecules. The intensity of cyto- and geno-toxicity depends on the physical and chemical properties of nanoparticles. Based on the literature survey, it is observed that the effects of nanoparticles on the growth, photosynthesis, and primary and secondary metabolism of plants are both positive and negative; the response of these processes to the nanoparticle was associated with the type of nanoparticle, the concentration within the tissue, crop species, and stage of growth. Future studies should focus on addressing the key knowledge gaps in understanding the responses of plants to nanoparticles at all levels through global transcriptome, proteome, and metabolome assays and evaluating nanoparticles under field conditions at realistic exposure concentrations to determine the level of entry of nanoparticles into the food chain and assess the impact of nanoparticles on the ecosystem.

Effect of Silver Nanoparticle Size on Antibacterial Activity

The ubiquitous use of products containing AgNPs results in the entry of nanoparticles into the environment. Both nanoparticles and Ag+ released upon their oxidative dissolution have a toxic effect on living microorganisms. The antibacterial activity of spherical silver nanoparticles of 10.8 ± 0.8 nm and 22.7 ± 2.2 nm in size stabilized by carbonate ions was studied against Escherichia coli and other bacteria. The biocidal action of silver increases as the particle size decreases. Analysis of these results and other known data made it possible to substantiate a linear proportional relationship between the minimum inhibitory concentration (MIC) or the half-maximal inhibitory concentration (IC50) and silver nanoparticle size and determine empirical parameters for this relationship. The antibacterial activity (toxicity) is directly proportional to the specific surface area of nanosized silver.

Uptake and translocation of nanoplastics in mono and dicot vegetables.

The excessive production and use of plastics increase the release of micro- and nanoplastics (MNPs) into the environment. In recent years, research has focused on the occurrence of MNPs in air, soil and water. Nevertheless, there is still a lack of knowledge regarding MNPs in plants. To determine the load, translocation of MNPs and their effects on metabolism, pak choi, tomato, radish and asparagus have been exposed with fluorescent-labelled poly(methyl methacrylate) or polystyrene (PS) MNPs. The entry of nanoparticles (NPs) of various sizes (100-500 nm) and surface modifications (unmodified, COOH or NH2) into plants has been demonstrated using confocal laser scanning microscopy (CLSM). The translocalization from root to shoot and the accumulation of NP in the intercellular spaces were regardless of the surface modification. In addition, metabolomics was used to evaluate metabolic changes induced by MNPs in pak choi. Changes in phenolic compounds, phytohormone derivatives and other classes of compounds known to be triggered by various environmental stresses have been identified. The present study demonstrates the uptake and translocalization of MNPs in edible parts of vegetables and may pose a hazard for humans.

Entry of nanoparticles into cells and tissues: status and challenges.

In this article we discuss how nanoparticles (NPs) of different compositions may interact with and be internalized by cells, and the consequences of that for cellular functions. A large number of NPs are made with the intention to improve cancer treatment, the goal being to increase the fraction of injected drug delivered to the tumor and thereby improve the therapeutic effect and decrease side effects. Thus, we discuss how NPs are delivered to tumors and some challenges related to investigations of biodistribution, pharmacokinetics, and excretion. Finally, we discuss requirements for bringing NPs into clinical use and aspects when it comes to usage of complex and slowly degraded or nondegradable NPs.

Electromigration effect of nano-Fe3O4 in concrete under chloride erosion environment

In order to improve the effectiveness of electro-migration repair technology, researchers have introduced new materials to address the adverse effects of electrochemical repair on concrete, such as interface softening in reinforced concrete. In this study, a dispersed solution of nano-Fe3O4 was selected as the anode electrolyte. Concrete specimens were subjected to electric treatment for repair, and the entry of nano particles into the concrete under the action of an external electric field was investigated. The microstructure and mechanical properties of the repaired concrete material were analyzed using techniques such as potentiodynamic polarization curve, chemical titration, scanning electron microscopy, energy spectrum analysis, mercury intrusion porosimetry, and pull-out test. The results showed that after 15 days of electrochemical nano-repair, the passivation film on the steel reinforcement was repaired, resulting in a 57 % reduction in corrosion rate and prevention of further chloride ingress, thus improving the corrosion resistance of the reinforcement. Furthermore, the electrochemical nano-repair did not affect the outward migration of chloride ions from the concrete, with a chloride removal efficiency as high as 72.6 %. When the treatment duration was 15 days and the current density was 3 A/m2, the bond strength exhibited the greatest improvement, with an increase of 99.15 %. Compared to electrochemical chloride removal, the electrochemical nano-repair reduced the porosity in the middle and inner layers by 17.8 % and 14.8 %, respectively. Microstructural analysis revealed that the electromigrated nano-Fe3O4 particles were uniformly dispersed within the concrete, replacing harmful byproducts and filling the pores.

Exploring Sustainable Agriculture with Nitrogen-Fixing Cyanobacteria and Nanotechnology.

The symbiotic relationship between nitrogen-fixing cyanobacteria and plants offers a promising avenue for sustainable agricultural practices and environmental remediation. This review paper explores the molecular interactions between nitrogen-fixing cyanobacteria and nanoparticles, shedding light on their potential synergies in agricultural nanotechnology. Delving into the evolutionary history and specialized adaptations of cyanobacteria, this paper highlights their pivotal role in fixing atmospheric nitrogen, which is crucial for ecosystem productivity. The review discusses the unique characteristics of metal nanoparticles and their emerging applications in agriculture, including improved nutrient delivery, stress tolerance, and disease resistance. It delves into the complex mechanisms of nanoparticle entry into plant cells, intracellular transport, and localization, uncovering the impact on root-shoot translocation and systemic distribution. Furthermore, the paper elucidates cellular responses to nanoparticle exposure, emphasizing oxidative stress, signaling pathways, and enhanced nutrient uptake. The potential of metal nanoparticles as carriers of essential nutrients and their implications for nutrient-use efficiency and crop yield are also explored. Insights into the modulation of plant stress responses, disease resistance, and phytoremediation strategies demonstrate the multifaceted benefits of nanoparticles in agriculture. Current trends, prospects, and challenges in agricultural nanotechnology are discussed, underscoring the need for responsible and safe nanoparticle utilization. By harnessing the power of nitrogen-fixing cyanobacteria and leveraging the unique attributes of nanoparticles, this review paves the way for innovative, sustainable, and efficient agricultural practices.

Impact of nanoparticles on human health and disease.

Nanoparticles (NPs) are small particles with a surface area ranging from 1 to 100 nm in diameter that are rampantly used in different fields, e.g., medicine, engineering, and others. Because of their unique properties, such as their tiny size, magnetic properties, quantum size effects, and macroscopic quantum tunnelling effects, they are crucial for a wide range of potential applications. NPs play a significant role in the treatment of vascular disorders, the production of vaccines, and the development of drug carriers for diverse therapies due to their bioavailability, targeting ability, and efficacy. However, significant risks to the environment and health are also associated with it. NPs cause necrotic plasma membrane rupture or apoptosis, which leads to cell death. NPs interfere with cell signalling, endosomal membranes, and organelles like the nucleus or mitochondria, affecting their function. NPs cause autophagic cell death, which causes a stress response and sterile inflammation. The primary routes for the entry of NPs into the human body are inhalation, ingestion, and skin contact. NPs accumulate in the respiratory system based on their size, shape, and surface properties. NPs can cause lung inflammation and fibrosis, disrupt the endocrine system by attaching to hormone receptors, and produce reactive oxygen species (ROS) associated with DNA damage, oligospermia, and male infertility. Carcinogenic properties of NPs cause mutations, apoptosis, and inflammatory responses. Collaborative research between ecologists and epidemiologists may enlighten ways to reduce the harmful effects of NPs.

Ultrastructural characteristics of the accumulation of iron nanoparticles in the intestine of Cyprinus carpio (Linnaeus, 1758) under aquaculture

During the development of nanotechnology, the production of many substances containing nanoparticles leads to the release of various nanoparticles into the environment, including the water ecosystem. The main goal of the current research was to study the ultrastructural characteristics of the entry and bioaccumulation of Fe3O4 nanoparticles in the small intestine of Cyprinus carpio (Linnaeus, 1758), as well as the pathomorphological changes in the fish organism. Two different doses (10 and 100 mg) of Fe3O4 nanoparticles were fed to fingerlings for 7 days and then intestinal samples were taken and studied. It was found that the extent of damages was boosted within the increment of nanoparticle concentration. The sequence and bioaccumulation of Fe3O4 nanoparticles in the small intestine of fish occurred as below: firstly, the nanoparticles passed into microvilli located in the apical part of enterocytes in the mucosa layer, from there into the cytoplasm of the epithelial cells, including cytoplasmatic organelles (nucleus, mitochondria, lysosomes, fat granules), and then into a lamina propria of the mucosa of the small intestine and passed into the endothelium of the blood vessels and to the erythrocytes of the vessels which located in the lumen. It was determined that although the nanoparticles were up to 30 nm in size, only particles with a maximum size of 20 nm could penetrate the intestinal wall. Thus, the release of Fe3O4 nanoparticles into the environment in high doses has a negative effect on the living ecosystem, including the body of fish living in the water.

Nanomanipulation of Ligand Nanogeometry Modulates Integrin/Clathrin-Mediated Adhesion and Endocytosis of Stem Cells.

Nanosubstrate engineering can be a biomechanical approach for modulating stem cell differentiation in tissue engineering. However, the study of the effect of clathrin-mediated processes on manipulating this behavior is unexplored. Herein, we develop integrin-binding nanosubstrates with confined nanogeometries that regulate clathrin-mediated adhesion- or endocytosis-active signaling pathways for modulating stem fates. Isotropically presenting ligands on the nanoscale enhances the expression of clathrin in cells, thereby facilitating uptake of dexamethasone-loaded nanoparticles (NPs) to boost osteogenesis of stem cells. In contrast, anisotropic ligand nanogeometry suppresses this clathrin-mediated NP entry by strengthening the association between clathrin and adhesion spots to reinforce mechanotransduced signaling, which can be abrogated by the pharmacological inhibition of clathrin. Meanwhile, inhibiting focal adhesion formation hinders cell spreading and enables a higher endocytosis efficiency. Our findings reveal the crucial roles of clathrin in both endocytosis and mechanotransduction of stem cells and provide the parameter of ligand nanogeometry for the rational design of biomaterials for tissue engineering.

Single-bubble sonoluminescence of aqueous suspensions of ZnS or Tb(acac)3·H2O nanoparticles

Aqueous suspensions of nanoparticles (below 50 nm in size) of ZnS or Tb(acac)3·H2O crystals were prepared by dispersion under multibubble sonolysis. Single-bubble sonoluminescence (SL) of these colloidal suspensions in an ultrasonic standing wave was found. For a ZnS suspension, the SL spectrum of a bubble moving at acoustic pressure pa = 1.29 bar, recorded with 12 nm resolution, exhibited a ZnS band with a maximum at 470 nm against the background of a wide continuum of bubble luminescence (200–700 nm). At a resolution of 1.2 nm, numerous lines of atomic (Zn, S) and ionic (S+, S2+, S3+) emitters were present in the 270–670 nm range. For a Tb(acac)3 suspension at 12 nm resolution, Tb3+ quasilines were detected at 488, 544, 585, and 618 nm (5D4 – 7Fj transitions, j = 6,5,4,3). At 1.2 nm resolution, no terbium atomic lines were found. The ZnS band and Tb3+ quasilines were present, although with a lower intensity (at a constant continuum intensity), in the SL spectra of suspensions for a stationary (pa = 1.07 bar) bubble. The atomic emitter lines for a stationary bubble were absent in the spectra of both suspensions. The ZnS band and Tb3+ quasilines in the SL spectra were similar to those in the photoluminescence (PL) spectra. However, the spectrum of a moving bubble in a Tb(acac)3 suspension differed from the PL spectrum in the relative intensities of the quasilines for some transitions. It was concluded that a non-equilibrium plasma was ignited in a stationary or moving bubble in suspensions under periodic compression of its gas content. This was the main source of luminescence during sonolysis, which was observed as thermal emission bursts in a plasma with a spectral continuum. In addition, sonophotoluminescence was generated as re-emission of the continuum luminescence partially absorbed by nanoparticles in suspensions; this occurred as flashes of ZnS or Tb3+ characteristic luminescence. Additionally, for a moving bubble, there was luminescence of these emitters associated with the entry of nanoparticles into the bubble and the collisional excitation of emitters in the plasma. In the case of a ZnS suspension, there was luminescence of atomic emitters (Zn, S) that formed upon decomposition and excitation of fragments of the initial emitter (ZnS) in a bubble plasma. The absence of a similar component in the SL spectrum of the Tb(acac)3 suspension may be attributable to low efficiency of the collisional excitation of terbium atoms, which were undoubtedly formed upon decomposition of nanoparticles in a bubble plasma. The emitters and mechanisms of the studied single-bubble sonoluminescence in colloidal suspensions were compared with those for the previously considered (J. Luminescence. 252 (2022) 119389) multibubble sonotriboluminescence in non-colloidal suspensions of ZnS or Tb(acac)3·H2O crystals.

A novel probe to assess cytosolic entry of exogenous proteins

Dendritic cells use a specialized pathway called cross-presentation to activate CD8+ T cells by presenting peptides from exogenous protein antigens on major histocompatibility complex class I molecules. Considerable evidence suggests that internalized antigens cross endocytic membranes to access cytosolic proteasomes for processing. The mechanism of protein dislocation represents a major unsolved problem. Here we describe the development of a sensitive reporter substrate, an N-glycosylated variant of Renilla luciferase fused to the Fc region of human IgG1. The luciferase variant is designed to be enzymatically inactive when glycosylated, but active after the asparagine to aspartic acid conversion that occurs upon deglycosylation by the cytosolic enzyme N-glycanase-1. The generation of cytosolic luminescence depends on internalization, deglycosylation, the cytosolic AAA-ATPase VCP/p97, and the cytosolic chaperone HSP90. By incorporating a T cell epitope into the fusion protein, we demonstrate that antigen dislocation into the cytosol is the rate-limiting step in cross-presentation. Currently, we are using this novel probe to determine the efficiency of the cytosolic entry of nanoparticles that co-encapsulate ddRLuc-Fc and mRNA. It will provide us with important information about mRNA delivery by those nanoparticles, potentially leading to a breakthrough in mRNA vaccine development.

Co-administration of Transportan Peptide Enhances the Cellular Entry of Liposomes in the Bystander Manner Both In Vitro and In Vivo.

Liposomes have been widely used as a drug delivery vector. One way to further improve its therapeutic efficacy is to increase the cell entry efficiency. Covalent conjugation with cell-penetrating peptides (CPPs) and other types of ligands has been the mainstream strategy to tackle this issue. Although efficient, it requires additional chemical modifications on liposomes, which is undesirable for clinical translation. Our previous study showed that the transportan (TP) peptide, an amphiphilic CPP, was able to increase the cellular uptake of co-administered, but not covalently coupled, metallic nanoparticles (NPs). Termed bystander uptake, this process represents a simpler method to increase the cell entry of NPs without chemical modifications. Here, we extended our efforts to liposomes. Our results showed that co-administration with the TP peptide improved the internalization of liposome into a variety of cell lines in vitro. This effect was also observed in primary cells, ex vivo tumor slices, and in vivo tumor tissues. On the other hand, this peptide-assisted liposome internalization did not apply to cationic CPPs, which were the main inducers for bystander uptake in previous studies. We also found that TP-assisted bystander uptake of liposome is receptor dependent, and its activity is more sensitive to the inhibitors of the macropinocytosis pathway, underlining the potential cell entry mechanism. Overall, our study provides a simple strategy based on TP co-administration to increase the cell entry of liposomes, which may open up new avenues to apply TP peptides in nanotherapeutics.

Bacteria-targeting photoactivated antibacterial nanosystem based on oligoalginate-protoporphyrin IX for plant disease treatment

To enhance bacteria-targeting and improve bactericidal activity, a novel GSH-responsive photodynamic antimicrobial nanosystem based on Alginate oligosaccharide-protoporphyrin IX (AOS-ss-PpIX) conjugates were constructed. The fluorescence self-quenching caused by the aggregation of PpIX groups into hydrophobic core could promote the photostability of PpIX and avoid the phototoxicity of the non-infected sites of the target plants. But once exposed to GSH stimulus, the recovery of high photodynamic activity were observed due to the destruction of the system and accompanied by the release of thiolated PpIX, and the photodynamic activity after 2 h was higher than that of PpIX under the same conditions. Furthermore the system showed more efficient photodynamic antibacterial capacity under light exposure. Moreover, the pot experiment also verified that the system showed outstanding control efficacy against cabbage soft rot caused by Erwinia carotovora Sclerotinia. Safety test exhibited that the size of nanoparticles can restrict the entry of nanoparticles into the plant cells to trigger photocytotoxicity. The design strategy provides a platform for promoting the utilization of photoactivated pesticides and reducing or avoiding their harm to target plants and the environment.

Self-fluorescence property of octa-arginine functionalized hydroxyapatite nanoparticles aids in studying their intracellular fate in R1 ESCs

Deciphering the endocytosis mechanisms of nanoparticle entry in cells is crucial to understand the fate of nanoparticles and the biological activity of the transported cargo. Such studies require the use of reporter agents such as fluorescent markers. Previously, we have reported the synthesis of self-fluorescent HAp nanoparticles as efficient nucleic acid delivery agents in prokaryotic and eukaryotic cells. Here, we show the application of biocompatible self-fluorescent nano delivery vehicle based on HAp and CPP- octa-arginine as an efficient system to study the mechanisms of intracellular fate of a gene delivery agent. The pathway of octa-arginine functionalized HAp NP (R8HNP) and HAp NP uptake in R1 ESCs was elucidated using confocal microscopy with the help of endocytic inhibitors. The NPs mainly enter R1 ESCs by clathrin mediated and macropinocytosis pathways. It was established that the NPs escape endosomal degradation by proton sponge effect owing to their ability to buffer the pH and trigger osmotic rupture. The functionalization of CPP, effectively enhanced the internalization and endosomal escape in R1 ESCs. The detailed results of these studies are outlined in this manuscript.

(Digital Presentation) Engineering Band Gap of Chalcogenide Nanomaterial-Polymer Composites

Over the last two decades, engineering the optical properties of nanoscale structures (nanowires, quantum dots, and nanotubes), i.e., band gap, absorption, and photoluminescence radiation, which can be manipulated in sulfide-based semiconductor materials, has received a lot of attention. Due to their tunable characteristics, these materials were introduced for potential applications ranging from medicine and communications to energy and various sensors (1). In addition, chemical synthesis methods provide the desired structure, material, reproducibility, and possibility of large-scale production, along with sustainable industrialization and foster innovation of these material systems. Polyvinyl-alcohol (PVA) is one of the functional polymers, in addition to the ability to stabilize the nanomaterial solution, which can change the optical properties of the material (2). Currently, the majority of sulfide-based nanomaterials are cadmium, lead, and silver, which have shown a wide range of applications. Here, PVA/CdS, PVA/PbS, and PVA/Ag2S nanocomposites were investigated as the desired composites. For optical studies, band gap, absorption, and photoluminescence irradiation of these material systems were performed. The structural and morphological properties were examined by scanning electron microscopy, DLS, and X-ray diffraction. The band gap value of synthesized nanoparticles in the polymer bed was 3.48, 3.08, and 2.27 eV for PVA/CdS, PVA/PbS, and PVA/Ag2S, respectively, whereas for pure PVA the band gap value was 4.75 eV. As shown in Figure 1, with the entry of nanoparticles into the polymer, a shift in the composite band gap can be seen that corresponds to an increase in absorption. Photoluminescence irradiations for polymer-nanoparticle composites showed that silver-polymer nanoparticles have intense irradiance at 405nm, while cadmium-polymer and lead-polymer composites have intense irradiance at 430nm and 500nm, respectively. An X-ray diffraction pattern was indicated for each of the crystals, confirming the presence of the expected crystal structure. The DLS of materials represents sizes of 150, 125, and 175 nm for PVA/CdS, PVA/PbS, and PVA/Ag2S. Besides, the structure of the material systems was examined by FE-SEM microscopy, which showed a homogeneous distribution of particles in the polymer and a cubic nanoparticle structure for PVA/PbS and a spherical for PVA/Ag2S and PVA/CdS. Our findings show that polymer-nanomaterial composites are potential candidates for use in sensors and solar energy cells, especially non-toxic Ag2S nanomaterials (3) that have already been documented as an emerging platform for in-vivo imaging.

Abstract 231: Monocyte-mimicking Nanoparticles For Atherosclerosis-targeted Therapy

Atherosclerosis, characterized by plaque buildup in arteries, is a major cause of cardiovascular mortality globally. Despite advances in diagnostics and interventions over the past few decades, the treatment options and outcomes remain far less than optimal. Nanotechnology has demonstrated emerging success in clinical settings; however, a potent targeted nanotherapeutic for atherosclerosis remains underdeveloped. In this study, we designed a new class of nanocarriers mimicking circulating monocyte features to enhance the site-specific delivery of theranostic agents for atherosclerosis. We first synthesized polymeric cores encapsulating a fluorescent payload with a modified nanoprecipitation method and cloaked the polymeric cores (NPs) with the plasma membrane fraction isolated from mouse monocytes. Our characterization results verified that NP cores are covered with a uniform lipid layer and that the resulting monocyte-mimicking nanoparticles (MNPs) retain the membrane proteins on their surface and have a similar value of zeta potential as monocytes. Both MNPs and NPs did not exhibit any hemotoxicity in vitro ; however, when incubated with cultured human vascular endothelial cells (ECs), MNPs showed a significantly higher uptake efficiency by ECs than NPs. Moreover, our in vivo studies with ApoE-knockout mice indicates that MNPs accumulated only in the atherosclerotic arteries but no other areas of the vasculature when administered intravenously. To summarize, our findings strongly support that monocyte membrane cloaking facilitates the nanoparticle attachment to atherosclerotic regions and enhances the entry of nanoparticles into the inflammatory endothelium in the arteries, suggesting that MNPs would serve as an excellent delivery strategy for targeted atherosclerosis therapy.

Different Effects of Reversible Electroporation-Mediated Fe3O4@AuNPs Delivery as Radiosensitizing Agents on Cancer Cells versus Normal Cells

Aim: In the present study, we sought to enhance the efficacy of radiotherapy via increasing the cellular uptake of Fe3O4@AuNPs as radiosensitizing agents using reversible electroporation, attaining a higher sensitivity for cancer cells to therapy-induced damage. Methods: The KB human nasopharyngeal carcinoma cell line was treated with different concentrations of gold-coated magnetic nanoparticles. The cells then received electroporation (750[Formula: see text]V/cm, 8 pulses for a duration 100[Formula: see text][Formula: see text]s with 100[Formula: see text]ms intervals) and radiotherapy (6MV X-ray, 2[Formula: see text]Gy). Control groups were carefully considered to assess the pure effect of both single and combinational therapeutic protocols. The MTT test and flow cytometry assay using Annexin V-PI kit were performed to evaluate potential effects on cell survival rate and to determine the induced level of apoptosis. Additionally, cellular uptake of nanoparticles was assessed and quantified using ICP-OES analysis. Results: Our study showed that nanoparticles and the applied procedure of electroporation had no considerable effects when utilized separately, but their combined application induced significant cell death ([Formula: see text]45%) and apoptosis ([Formula: see text]17%). Besides, the application of Fe3O4@AuNPs in the presence of electric field, 24[Formula: see text]h before the radiotherapy of tumor cells enhanced the cancer cell death ([Formula: see text]53%) as well as apoptosis rate ([Formula: see text]33%). The same scenario was also observed with normal HGF human gingival fibroblasts, confirmed by significantly lower levels of cell death and apoptosis. Conclusion: It can be concluded that electric fields at low voltage levels may significantly and selectively enhance the entry of nanoparticles into cancer cells, thereby accentuating the sensitivity of these cells to nanoparticle-mediated radiation therapy.

Biomimetic Nanoparticle Drug Delivery Systems to Overcome Biological Barriers for Therapeutic Applications.

Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.

Cellular Process of Polystyrene Nanoparticles Entry into Wheat Roots.

Nanoscale plastic particles are widely found in the terrestrial environment and being increasingly studied in recent years. However, the knowledge of their translocation and accumulation mechanism controlled by nanoplastic characterizations in plant tissues is limited, especially in plant cells. Here, 20 mg L-1 polystyrene nanoparticles (PS NPs) with different sizes and amino/carboxy groups were employed to investigate the internalization process in wheat roots and cells. From the results, we found that the uptake of small-size PS NPs in the root tissues was increased compared to that of large-size ones, but no PS NPs were observed in the vascular cylinder. Similar results were observed in their cellular uptake process. Besides, the cell wall could block the entry of large-size PS NPs while the cell membrane could not. The -NH2 group on the PS NPs surface could benefit their tissular/cellular translocation compared to the -COOH group. The internalization of PS NPs was controlled by both particle size and surface functional group, and the size should be the primary factor. Our findings offer important information for understanding the PS NPs behaviors in plant tissues, especially at the cellular level, and assessing their potential risk to food safety, quality, and agricultural sustainability.

Synergistic Entry of Individual Nanoparticles into Mammalian Cells Driven by Free Energy Decline and Regulated by Their Sizes.

Cell entry is one of the common prerequisites for nanomaterial applications. Despite extensive studies on a homogeneous group of nanoparticles (NPs), fewer studies have been performed when two or more types of NPs were coadministrated. We previously described a synergistic cell entry process for two heterogeneous groups of NPs, where NPs functionalized with TAT (transactivator of transcription) peptide (T-NPs) stimulate the cellular uptake of coadministered unfunctionalized NPs (bystander NPs, B-NPs). Here, we show that the synergistic cell entry of NPs is driven by free energy decline and depends on B-NP sizes. Simulations showed that when separately placed initially, two NPs first move toward each other instead of initiating cell entry individually. Only T-NP invokes an inward bending of membrane mimicking endocytosis, which attracts the nearby NPs into the same "vesicle". A two-phase free energy decline of the entire system occurred as two NPs get closer until contact, which is likely the thermodynamic driver for synergistic NP coentry. Experimentally, we found that T-NPs increase the apparent affinity of B-NPs to plasma membrane, suggesting that T-NPs help B-NPs "trapped" in the endocytic vesicles. Next, we varied the sizes of B-NPs and found that bystander activity peaks around 50 nm. Simulations also showed that the size of B-NPs influences the free energy decline, and thus the tendency and dynamics of NP coentry. These efforts provide a system to further understand the synergistic cell entry among individual NPs or multiple NP types on a biophysical basis and shed light on the future design of nanostructures for intracellular delivery.