Carbene-coated metal nanoparticles for in vivo applications.

N-Heterocyclic carbenes (NHC) are well-recognized ligands of choice for preparing robust transition metal species. However, their use for fabrication of biomedically relevant nanoparticles has been limited to the synthesis of non-targeted particles showing increased tolerance to different aqueous coagulants. In this work, the first example of carbene-coated metal nanoparticles suitable for in vivo applications is presented. Directed design of a novel biscarbene NHC ligand allowed to prepare the first magnetite/gold (Fe3O4@AuNP@NHC) nanostructures and carbene gold (AuNP@NHC) nanoparticles with significant stability in aqueous solutions and enhanced ability to form bioconjugates. Furthermore, these nanoparticles exhibit an extraordinary property for inorganic nanoparticles: they can endure several additive-free air drying/redispersion cycles without deterioration of their colloidal behavior. Bioconjugated AuNP@NHC and multimodal Fe3O4@AuNP@NHC demonstrated a successful performance in three distinct applications: lateral flow tests, specific cancer cell targeting, and bioimaging. Thus, the results show the notable advantages of the N-heterocyclic carbene coating of inorganic nanoparticles and their utility for complex biomedical applications.

A do-it-yourself benchtop device for highly scalable flow synthesis of protein-based nanoparticles.

Synthesis of nanoparticles is typically carried out in batch procedures, which offer limited control of parameters, and a narrow range of possible batch volumes. In contrast, flow synthesis systems, usually having a microfluidic chip as a crucial part, are devoid of these drawbacks. However, large scale devices - millifluidic systems - may offer several advantages over microfluidic systems, such as easier and cheaper production, enhanced throughput, and reduced channel clogging. Here we report a millifluidic system for the generation of protein nanoparticles, using the flow format of the original swift thermal formation technology (STF), which can process batch volume ranging from 100 µl to any practically significant amount. Capabilities of the system are demonstrated with model synthesis of Epirubicin-encapsulated BSA nanoparticles. A better degree of scalability of the synthesis over batch procedure is shown: with a 10-fold working volume increase, hydrodynamic diameter and loading capacity changed by only 10 % and 1 % respectively, compared to 60 % and 30 % for the batch synthesis. Additionally, we provide all engineering drawings, electrical circuits, programming code and nuances of assembly and operation, so that our findings can be easily reproduced. The ease of construction of the device and the superior characteristics of the resulting nanoparticles compared to the batch method indicate application potential in both the biomedical research and industrial spheres.

Carotid endarterectomy for symptomic and asymptomic stenosis: Report of 65388 cases (Russian register).

AIM: Analysis of in-hospital and long-term results of carotid endarterectomy in patients with asymptomatic and symptomatic stenoses. MATERIALS AND METHODS: The sample was formed by completely including all cases of carotid endarterectomy (n = 65,388) performed during the period from May 1, 2015 to November 1, 2023. Depending on the symptomatic/asymptomatic nature of the stenosis, all patients were divided into two groups: group 1 - n = 39,172 (75.2%) - patients with asymptomatic stenosis; Group 2 - n = 26216 (24.8%) - patients with symptomatic stenosis. The postoperative follow-up period was 53.5 ± 31.4 months. RESULTS: In the hospital postoperative period, the groups were comparable in the incidence of death (group 1: n = 164 (0.41%); group 2: n = 124 (0.47%); p = .3), transient ischemic attack (group 1: n = 116 (0.29%); group 2: n = 88 (0.33%); p = .37), myocardial infarction (group 1: n = 32 (0.08%); group 2: n = 19 (0.07%); p = .68), thrombosis of the internal carotid artery (group 1: n = 8 (0.02%); group 2: n = 2 (0.007%); p = 0, 19), bleeding (group 1: n = 58 (0.14%); group 2: n = 33 (0.12%); p = .45). In group 2, ischemic stroke developed statistically more often (group 1: n = 328 (0.83%); group 2: n = 286 (1.09%); p = .001), which led to a higher value of the combined endpoint (group 1: n = 640 (1.63%); group 2: n = 517 (1.97%); p = .001). In the long-term postoperative period, the groups were comparable in cases of death (group 1: n = 65 (0.16%); group 2: n = 41 (0.15%); p = .76) and death from cardiovascular causes (group 1: n = 59 (0.15%); group 2: n = 33 (0.12%); p = .4). A greater number of ischemic strokes were detected in patients of group 2 (group 1: n = 213 (0.54%); group 2: n = 187 (0.71%); p = .006). In group 1, hemodynamically significant restenosis (≥70%) of the internal carotid artery was more often diagnosed (group 1: n = 974 (2.49%); group 2: n = 351 (1.34%); p < .0001) and myocardial infarction (group 1: n = 66 (0.16%); group 2: n = 34 (0.13%); p < .0001). When analyzing stroke-free survival, analysis of Kaplan-Meier curves showed that a statistically larger number of strokes were diagnosed in group 2 (p < .0001). CONCLUSION: Due to the fact that the patients were initially not comparable for a number of indicators, to achieve balance, we applied propensity score matching analysis. Thus, group 1 consisted of 24,381 patients, and group 2 consisted of 17,219 patients. In the hospital postoperative period, statistically significant differences were obtained only in the combined end point, which was greater in group 2 (group 1: n = 465 (1.9%); group 2: n = 382 (2.2%); p = .02). In the long-term follow-up period, after applying propensity score matching, no statistically significant differences were obtained between groups.

The influence of various polymer coatings on the in vitro and in vivo properties of PLGA nanoparticles: Comprehensive study.

Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) with various surface chemistry are widely used in biomedicine for theranostic applications. The nature of the external coating of nanoparticles has a significant influence on their efficiency as drug carriers or visualization agents. However, information about the mechanisms of nanoparticle accumulation in tumors and the influence of their surface properties on biodistribution is scarce due to the lack of systematic evaluation. Here we investigate the effect of different polymer coatings of the surface on in vitro and in vivo properties of PLGA nanoparticles. Namely, cell binding efficiency, cytotoxicity, efficiency of fluorescent bioimaging, and tumor accumulation were tested. The highest binding efficiency in vitro and cytotoxicity were observed for positively charged polymers. Interestingly, in vivo fluorescent visualization of tumor-bearing mice and quantitative measurements of biodistribution of magnetite-loaded nanoparticles indicated different dependences of accumulation in tumors on the coating of PLGA nanoparticles. This means that nanoparticle surface properties can simultaneously enhance imaging efficiency and decrease quantitative accumulation in tumors. The obtained data demonstrate the complexity of the dependence of nanoparticles' effectiveness for theranostic applications on surface features. We believe that this study will contribute to the rational design of nanoparticles for effective cancer diagnostics and therapy.

Hospital and long-term results of carotid endarterectomy in patients with different severity of coronary artery lesion according to syntax score.

AIM: Analysis of in-hospital and long-term results of carotid endarterectomy (CEE) in patients with different severity of coronary atherosclerosis. MATERIAL AND METHODS: This comparative, retrospective, open study for the period from January 2013 to April 2020 included 1719 patients operated on for occlusive-stenotic lesions of the internal carotid arteries (ICA). Classical and eversion CEA were used as revascularization strategies. The criteria for inclusion in the study were: 1. Presence of coronary angiography within six months before the present CEE; 2. A history of myocardial revascularization in patients with severe coronary lesions. Depending on the severity of coronary atherosclerosis, all patients were divided into 3 groups: Group 1-871 (50.7 %) patients - with the presence of hemodynamically significant stenosis of the coronary arteries (CA) with a history of myocardial revascularization; Group 2-496 (28.8 %) patients - with the presence of hemodynamically insignificant lesions of the coronary artery (up to 70 %, not inclusive, and the trunk of the left coronary artery, up to 50 %, not inclusive); Group 3-352 (20.5 %) patients - without signs of atherosclerotic lesions of the coronary artery. In group 1, the observation period was 56.8±23.2 months, in group 2-62.0±15.6 months, in group 3-58.1±20.4 months. RESULTS: During the hospital observation period, there were no significant intergroup differences in the number of complications. All cardiovascular events were detected in isolated cases. The most common injury was damage to the cranial nerves, diagnosed in every fifth patient in the total sample. The combined endpoint (CET), including death + myocardial infarction (MI) + acute cerebrovascular accident/transient ischemic attack (stroke/TIA), was 0.75 % (n=13). In the long-term follow-up period, when comparing survival curves, group 3 revealed the largest number of ischemic strokes (p = 0.007), myocardial infarction (p = 0.03), and CCT (p = 0.005). There were no intergroup differences in the number of deaths (p=0.62). CONCLUSION: The results of the study showed that there was no significant intergroup difference in the development of complications at the hospital postoperative stage. However, in the long-term follow-up period, a group of patients with isolated lesions of the ICA demonstrated a rapid increase in the number of MI, stroke/TIA, and a combined endpoint, which was apparently associated with low compliance and progression of atherosclerosis in previously unaffected arteries.

Surface Characteristics Affect the Properties of PLGA Nanoparticles as Photothermal Agents.

Photothermal therapy is one of the most promising and rapidly developing fields in modern oncology due to its high efficiency, localized action, and minimal invasiveness. Polymeric nanoparticles (NPs) incorporating low molecular-weight photothermal dyes are capable of delivering therapeutic agents to the tumor site, releasing them in a controlled manner, and providing tumor treatment under external light irradiation. The nanoparticle synthesis components are critically important factors that influence the therapeutically significant characteristics of polymeric NPs. Here, we show the impact of stabilizers and solvents used for synthesis on the properties of PLGA NPs for photothermal therapy. We synthesized PLGA nanocarriers using the microemulsion method and varied the nature of the solvent and the concentration of the stabilizer-namely, chitosan oligosaccharide lactate. A phthalocyanine-based photosensitizer, which absorbs light in the NIR window, was encapsulated in the PLGA NPs. When mQ water was used as a solvent and chitosan oligosaccharide lactate was used at a concentration of 1 g/L, the PLGA NPs exhibited highly promising photothermal properties. The final composite of the nanocarriers demonstrated photoinduced cytotoxicity against EMT6/P cells under NIR laser irradiation in vitro and was suitable for bioimaging.

Comparative Study of Nanoparticle Blood Circulation after Forced Clearance of Own Erythrocytes (Mononuclear Phagocyte System-Cytoblockade) or Administration of Cytotoxic Doxorubicin- or Clodronate-Loaded Liposomes.

Recent developments in the field of nanomedicine have introduced a wide variety of nanomaterials that are capable of recognizing and killing tumor cells with increased specificity. A major limitation preventing the widespread introduction of nanomaterials into the clinical setting is their fast clearance from the bloodstream via the mononuclear phagocyte system (MPS). One of the most promising methods used to overcome this limitation is the MPS-cytoblockade, which forces the MPS to intensify the clearance of erythrocytes by injecting allogeneic anti-erythrocyte antibodies and, thus, significantly prolongs the circulation of nanoagents in the blood. However, on the way to the clinical application of this approach, the question arises whether the induced suppression of macrophage phagocytosis via the MPS-cytoblockade could pose health risks. Here, we show that highly cytotoxic doxorubicin- or clodronate-loaded liposomes, which are widely used for cancer therapy and biomedical research, induce a similar increase in the nanoparticle blood circulation half-life in mice as the MPS-cytoblockade, which only gently and temporarily saturates the macrophages with the organism's own erythrocytes. This result suggests that from the point of view of in vivo macrophage suppression, the MPS-cytoblockade should be less detrimental than the liposomal anti-cancer drugs that are already approved for clinical application while allowing for the substantial improvement in the nanoagent effectiveness.

Causal factors of work-related chemical eye injuries reported to the Dutch Poisons Information Center.

This study investigated the circumstances of chemical occupational eye exposures reported to the Dutch Poisons Information Center. During a 1-year prospective study, data were collected through a telephone survey of 132 victims of acute occupational eye exposure. Victims were often exposed to industrial products (35%) or cleaning products (27%). Most patients developed no or mild symptoms. Organizational factors (such as lack of work instructions (52%)), and personal factors (such as time pressure and fatigue (50%), and not adequately using personal protective equipment (PPE, 14%), were the main causes of occupational eye exposures. Exposure often occurred during cleaning activities (34%) and personal factors were reported more often during cleaning (67%) than during other work activities (41%). Data from Poison Control Centers are a valuable source of information, enabling the identification of risk factors for chemical occupational eye exposure. This study shows that personal factors like time pressure and fatigue play a significant role, although personal factors may be related to organizational issues such as poor communication. Therefore, risk mitigation strategies should focus on technical, organizational, and personal factors. The need to follow work instructions and proper use of PPE should also have a prominent place in the education and training of workers.

Vertebral triangle of doctor A.N. Kazantsev - double vertebral artery in V3 segment.

We have described a variant of the structure of the vertebral artery. In the V3 segment, the vertebral artery bifurcated and then joined again. This building looks like a triangle. Such anatomy has not been previously described in the world literature. By the right of the first description, this anatomical formation was called the «vertebral triangle of Dr A.N. Kazantsev¼. This discovery was made during stenting of the V4 segment of the left vertebral artery in the most acute period of stroke.

Targeted Two-Step Delivery of Oncotheranostic Nano-PLGA for HER2-Positive Tumor Imaging and Therapy In Vivo: Improved Effectiveness Compared to One-Step Strategy.

Therapy for aggressive metastatic breast cancer remains a great challenge for modern biomedicine. Biocompatible polymer nanoparticles have been successfully used in clinic and are seen as a potential solution. Specifically, researchers are exploring the development of chemotherapeutic nanoagents targeting the membrane-associated receptors of cancer cells, such as HER2. However, there are no targeting nanomedications that have been approved for human cancer therapy. Novel strategies are being developed to alter the architecture of agents and optimize their systemic administration. Here, we describe a combination of these approaches, namely, the design of a targeted polymer nanocarrier and a method for its systemic delivery to the tumor site. Namely, PLGA nanocapsules loaded with a diagnostic dye, Nile Blue, and a chemotherapeutic compound, doxorubicin, are used for two-step targeted delivery using the concept of tumor pre-targeting through the barnase/barstar protein "bacterial superglue". The first pre-targeting component consists of an anti-HER2 scaffold protein, DARPin9_29 fused with barstar, Bs-DARPin9_29, and the second component comprises chemotherapeutic PLGA nanocapsules conjugated to barnase, PLGA-Bn. The efficacy of this system was evaluated in vivo. To this aim, we developed an immunocompetent BALB/c mouse tumor model with a stable expression of human HER2 oncomarkers to test the potential of two-step delivery of oncotheranostic nano-PLGA. In vitro and ex vivo studies confirmed HER2 receptor stable expression in the tumor, making it a feasible tool for HER2-targeted drug evaluation. We demonstrated that two-step delivery was more effective than one-step delivery for both imaging and tumor therapy: two-step delivery had higher imaging capabilities than one-step and a tumor growth inhibition of 94.9% in comparison to 68.4% for the one-step strategy. The barnase*barstar protein pair has been proven to possess excellent biocompatibility, as evidenced by the successful completion of biosafety tests assessing immunogenicity and hemotoxicity. This renders the protein pair a highly versatile tool for pre-targeting tumors with various molecular profiles, thereby enabling the development of personalized medicine.

Non-complementary strand commutation as a fundamental alternative for information processing by DNA and gene regulation.

The discovery of the DNA double helix has revolutionized our understanding of data processing in living systems, with the complementarity of the two DNA strands providing a reliable mechanism for the storage of hereditary information. Here I reveal the 'strand commutation' phenomenon-a fundamentally different mechanism of information storage and processing by DNA/RNA based on the reversible low-affinity interactions of essentially non-complementary nucleic acids. I demonstrate this mechanism by constructing a memory circuit, a 5-min square-root circuit for 4-bit inputs comprising only nine processing ssDNAs, simulating a 572-input AND gate (surpassing the bitness of current electronic computers), and elementary algebra systems with continuously changing variables. Most importantly, I show potential pathways of gene regulation with strands of maximum non-complementarity to the gene sequence that may be key to the reduction of off-target therapeutic effects. This Article uncovers the information-processing power of the low-affinity interactions that may underlie major processes in an organism-from short-term memory to cancer, ageing and evolution.

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism.

Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design.

Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides.

Active targeting of tumors is believed to be the key to efficient cancer therapy and accurate, early-stage diagnostics. Active targeting implies minimized off-targeting and associated cytotoxicity towards healthy tissue. One way to acquire active targeting is to employ conjugates of therapeutic agents with ligands known to bind receptors overexpressed onto cancer cells. The integrin receptor family has been studied as a target for cancer treatment for almost fifty years. However, systematic knowledge on their effects on cancer cells, is yet lacking, especially when utilized as an active targeting ligand for particulate formulations. Decoration with various integrin-targeting peptides has been reported to increase nanoparticle accumulation in tumors ≥ 3-fold when compared to passively targeted delivery. In recent years, many newly discovered or rationally designed integrin-binding peptides with excellent specificity towards a single integrin receptor have emerged. Here, we show a comprehensive analysis of previously unreviewed integrin-binding peptides, provide diverse modification routes for nanoparticle conjugation, and showcase the most notable examples of their use for tumor and metastases visualization and eradication to date, as well as possibilities for combined cancer therapies for a synergetic effect. This review aims to highlight the latest advancements in integrin-binding peptide development and is directed to aid transition to the development of novel nanoparticle-based theranostic agents for cancer therapy.

Acute occupational exposures reported to the Dutch Poisons Information Center: a prospective study on the root causes of incidents at the workplace.

BACKGROUND: Hazardous substances at the workplace can cause a wide variety of occupational incidents. This study aimed to investigate the nature and circumstances of acute occupational intoxications reported to the Dutch Poisons Information Center. METHODS: During a one-year prospective study, data on the circumstances and causes of the incident, the exposure(s) and clinical course, were collected by a telephone survey with victims of an acute occupational intoxication. RESULTS: We interviewed 310 patients. Most incidents occurred in industry (25%), building and installation industry (14%) and agriculture (10%). Patients were often exposed via multiple routes. Inhalation was the most common route of exposure (62%), followed by ocular (40%) and dermal contact (33%). Acids and alkalis were often involved. Exposure often occurred during cleaning activities (33%). The main root causes of these accidents were: technical factors such as damaged packaging (24%) and defective apparatus (10%), organizational factors such as lack of work instructions (44%) and poor communication or planning (31%), and personal factors such as disregarding work instructions (13%), not (adequately) using personal protective equipment (12%) and personal circumstances (50%) such as inaccuracy, time pressure or fatigue. The majority of the patients only reported mild health effects and recovered quickly (77% within 1 week). CONCLUSIONS: Poison Center data on occupational exposures provide an additional source of knowledge and an important basis for poisoning prevention strategies related to hazardous substances at the workplace. These data are useful in deciding which risk mitigation measures are most needed in preventing future workplace injuries.

C60 Fullerene Clusters Stabilize the Biologically Inactive Form of Topotecan.

There is a range of experimental proofs that biologically relevant compounds change their activity in the presence of C60 fullerene clusters in aqueous solution, which most frequently act as a nanoplatform for drug delivery. Inspired by this evidence, we made an effort to investigate the interaction of fullerene clusters with the antibiotic topotecan (TPT). This study proceeded in three steps, namely, UV/vis titration to confirm complexation and in vitro assays on proliferating and nonproliferating cells to elucidate the role of C60 fullerene in the putative change in TPT activity. Surprisingly, although the nonproliferating cell assay is consistent with the titration data and confirms complex formation, it contradicted the results of the proliferating cell assay. The latter showed that the mixture of TPT and fullerene affects the cells in the same way as pure TPT, as if there were no fullerenes in solution at all, whereas the action of TPT was expected to be enhanced. We explained this contradiction by the specific stabilization of the biologically inactive carboxylate form of the antibiotic adsorbed in the alkaline shell of large fullerene clusters, which leads to neutralization of the drug delivery function and almost zero net biological effect of the antibiotic in vitro. The practical outcome of the work is that fullerene clusters can be used for the selective delivery of pH-sensitive drug forms.

Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission.

Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated. Here we show targeted photothermal therapy of solid tumors with 35 nm HER2-targeted Ag NPs, which were produced by the green synthesis using an aqueous extract of Lavandula angustifolia Mill. Light irradiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °C in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold polypeptide, affibody ZHER2:342, which recognizes a clinically relevant oncomarker HER2. The conjugation was mediated by the PEG linker to obtain Ag-PEG-HER2 nanoparticles. Flow cytometry tests showed that Ag-PEG-HER2 particles successfully bind to HER2-overexpressing cells with a specificity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed efficient internalization of Ag-PEG-HER2 into cells in less than 2 h of incubation. Cytotoxicity assays demonstrated effective cell death upon exposure to Ag-PEG-HER2 and irradiation, caused by the production of reactive oxygen species. Xenograft tumor therapy with Ag-PEG-HER2 particles in vivo resulted in full primary tumor regression and the prevention of metastatic spread. Thus, for the first time, we have shown that HER2-directed plasmonic Ag nanoparticles are effective sensitizers for targeted photothermal oncotherapy.

Materials synthesis at terapascal static pressures.

Theoretical modelling predicts very unusual structures and properties of materials at extreme pressure and temperature conditions1,2. Hitherto, their synthesis and investigation above 200 gigapascals have been hindered both by the technical complexity of ultrahigh-pressure experiments and by the absence of relevant in situ methods of materials analysis. Here we report on a methodology developed to enable experiments at static compression in the terapascal regime with laser heating. We apply this method to realize pressures of about 600 and 900 gigapascals in a laser-heated double-stage diamond anvil cell3, producing a rhenium-nitrogen alloy and achieving the synthesis of rhenium nitride Re7N3-which, as our theoretical analysis shows, is only stable under extreme compression. Full chemical and structural characterization of the materials, realized using synchrotron single-crystal X-ray diffraction on microcrystals in situ, demonstrates the capabilities of the methodology to extend high-pressure crystallography to the terapascal regime.

Adsorption of Polar Species at Crude Oil-Water Interfaces: the Chemoelastic Behavior.

We investigate the formation and properties of crude oil/water interfacial films. The time evolution of interfacial tension suggests the presence of short and long timescale processes reflecting the competition between different populations of surface-active molecules. We measure both the time-dependent shear and extensional interfacial rheology moduli. Late-time interface rheology is dominated by elasticity, which results in visible wrinkles on the crude oil drop surface upon interface disturbance. We also find that the chemical composition of the interfacial films is affected by the composition of the aqueous phase that it has contacted. For example, sulfate ions promote films enriched with carboxylic groups and condensed aromatics. Finally, we perform solution exchange experiments and monitor the late-time film composition upon the exchange. We detect the film composition change upon replacing chloride solutions with sulfate-enriched ones. To the best of our knowledge, we are the first to report the composition alteration of aged crude oil films. This finding might foreshadow an essential crude oil recovery mechanism.

Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor.

The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite - a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.