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X-ray computed tomography (CT), as one of the most widely used noninvasive imaging modalities, can provide three-dimensional anatomic details with high resolution, which plays a key role in disease diagnosis and treatment assessment. However, although they are the most prevalent and FDA-approved contrast agents, iodinated water-soluble molecules still face some challenges in clinical applications, such as fast clearance, serious adverse effects, nonspecific distribution, and low sensitivity. Because of their high biocompatibility, tunable designability, controllable biodegradation, facile synthesis, and modification capability, the polymers have demonstrated great potential for efficient delivery of iodinated contrast agents (ICAs). Herein, we comprehensively summarized the applications of multifunctional polymeric materials for ICA delivery in terms of increasing circulation time, decreasing nephrotoxicity, and improving the specificity and sensitivity of ICAs for CT imaging. We mainly focused on various iodinated polymers from the aspects of preparation, functionalization, and application in medical diagnosis. Future perspectives for achieving better imaging and clinical translation are also discussed to motivate new technologies and solutions.

New modified coagulation factor VIII (FVIII) and factor IX (FIX) products have been designed to improve the treatment of individuals with hemophilia A and B by increasing the interval between dosing. Although these FVIII and FIX molecules have been structurally modified to improve the circulation time, the changes have also influenced their behavior in functional assays in comparison with traditional plasma-derived or recombinant coagulation factors. The assignment of potencies for these products can be problematic because discordance in factor activity values between the commonly used one-stage clotting (OC) and chromogenic substrate (CS) assays is often observed. Discrepancies in potency assay values also exist when different assay kits and reagents are used in the same assay type. Ideally, all FVIII and FIX products should be calibrated against the World Health Organization (WHO) International Standards (IS) because the assignment of potencies in International Units (IU) helps maintain treatment tradition and meaningful references for manufacturers, patients, and clinicians. The discrepant measurements, attributed to the modified structural and functional properties of these products, are manifested in their lack of commutability with the WHO IS for FVIII or FIX. Herein, we discuss the considerations upon which an assay is chosen for potency assignment and post-administration monitoring of a new factor product, which include the validity of the assay calibrated with the IS, the meaning of the potency values in IU, standards of care for patients, clinical relevance between the assigned potency value and recovery value from clinical labs, and patient safety.

Severe accidental hypothermia carries high mortality and morbidity and is often treated with invasive extracorporeal methods. Continuous veno-venous hemodiafiltration (CVVHDF) is widely available in intensive care units. We sought to provide theoretical basis for CVVHDF use in rewarming of hypothermic patients. CVVHDF system was used in the laboratory setting. Heat balance and transferred heat units were evaluated for the system without using blood. We used 5L of crystalloid solution at the temperature of approximately 25°C, placed in a thermally insulated tank (representing the "central compartment" of a hypothermic patient). Time of warming the central compartment from 24.9 to 30.0°C was assessed with different flow combinations: "blood" (central compartment fluid) 50 or 100 or 150 mL/min, dialysate solution 100 or 1500 mL/h, and substitution fluid 0 or 500 mL/h. The total circulation time was 1535 minutes. There were no differences between heat gain values on the filter depending on blood flow (P = .53) or dialysate flow (P = .2). The mean heating time for "blood" flow rates 50, 100, and 150 mL/min was 113.7 minutes (95% CI, 104.9-122.6 minutes), 83.3 minutes (95% CI, 76.2-90.3 minutes), and 74.7 minutes (95% CI, 62.6-86.9 minutes), respectively (P

Short half-life is one of the main causes of drug attrition in clinical development, which also leads to the failure of many leading compounds and hits to become drug candidates. Nowadays, nanomaterials have been applied to drug development to address this problem. In fact, the clinical application of nanoparticles (NPs) is severely limited due to their rapid elimination by the reticuloendothelial system (RES) in vivo. In this paper, we aim to summarize representative strategies on prolonging the circulation time for bridging the gap between excellent pharmaceutics and proper half-life and encourage clinical translation.

In this article, move contrast X-ray imaging (MCXI) based on high-brightness synchrotron radiation is developed. Experiments with live rodents demonstrate the practicability of the MCXI method for sensitive and intact imaging of microvessels in vivo., Early stages of diseases, including stroke, hypertension, angiogenesis of tumours, spinal cord injuries, etc., are closely associated with the lesions of microvasculature. Rodent models of human vascular diseases are extensively used for the preclinical investigation of the disease evolution and therapy with synchrotron radiation. Therefore, non-invasive and in vivo X-ray imaging with high sensitivity and clarity is desperately needed to visualize the microvessels in live-animal models. Contrast agent is essential for the in vivo X-ray imaging of vessels and angiomatous tissue. Because of the non-rigid motion of adjacent tissues, the short circulation time and the intermittent flow of contrast agents in vessels, it is a great challenge for the traditional X-ray imaging methods to achieve well defined images of microvessels in vivo. In this article, move contrast X-ray imaging (MCXI) based on high-brightness synchrotron radiation is developed to overcome the intrinsic defects in conventional methods. Experiments with live rodents demonstrate the practicability of the MCXI method for sensitive and intact imaging of microvessels in vivo.

Chemotherapy is the most commonly used treatment for cancer. However, due to their short circulation time and lack of specific biological distribution, chemotherapeutic drugs cause severe systemic toxicity. Using the agents specifically binding to the targeted molecules might resolve this dilemma. Aptamers can directly connect with the drugs or couple with the nano-carrier to reduce systemic toxicity. In this review, we elucidated the definition, characteristics and screening process of aptamers. The methods of drug delivery by aptamers were illustrated in details. Furthermore, clinical application of aptamers in recent years was briefly summarized and its long-term prospects were put forward.

The long circulation time and targeting drug delivery at tumor sites are still the main challenges of nanodrug delivery systems for antitumor activity. Herein, a cancer cell membrane-coated biomimetic nanodrug delivery system was fabricated. The paclitaxel (PTX)-loaded poly(lactic acid) (PLA) nanoparticles (PPNs) were used as the inner cores and 4T1 cancer cell membranes were coated on the surface of PPNs as the outer shells. The biomimetic platform was noted as CPPNs. The CPPNs exhibited proper sizes for the enhanced permeability and retention (EPR) effect and could maintain stability in a simulated physiological environment. The CPPNs exhibited a better antitumor effect than PPNs and free PTX

A peptic ulcer is a chronic and recurrent disease, massively effect on the morbidity and mortality and almost 20% of the world human population experiences from this illness. The main factors lead to peptic ulcer is the infection of Helicobacter pylori bacteria and regular intake of non-steroidal anti-inflammatory drugs (NSAIDs). Huge development has been accomplished in deciding the pathogenesis of this disease and finding the right biomarkers are mandatory with understanding the current scenario. The existence and form of ulcers cannot be anticipated precisely from the signs and the differential diagnosis is comprehensive. Ultimately, diagnostics on H. pylori have been in front of the beneficial health of human and a special focus in the future. On the other hand, nanoencapsulation is an advanced methodology, can be applied in peptic ulcer treatment from the natural sources. Indeed, nanocellulose particles have been proposed and studied as novel formulations to enhance the stability and solubility of phytochemicals, improve their absorption, protect them from untimely degradation in the body and lengthen their circulation time. Merging the current prospects of diagnostics and nanotechnological approaches are necessary for the remedy from peptic ulcer.

Acute stent recoil or radial collapse of a stent is a rare phenomenon leading to subsequent acute stent thrombosis or in-stent restenosis as delayed sequelae. Reduced strut thickness, a larger stent/vessel ratio, and a larger balloon/stent ratio are factors leading to stent recoil. Here, we report a case of acute recoil or radial collapse of Promus Element Plus, a third-generation everolimus-eluting stent with thin stent struts in a 66 year-old male who underwent bifurcation percutaneous coronary intervention of left anterior descending artery (LAD) and diagonal branch (D1). Following kissing balloon inflation at 16 atm pressure after deployment of stents in LAD and D1, acute radial collapse of stent in proximal LAD was noted. It was successfully bailed out by further multiple, short sequential inflations using same size noncompliant balloon. Acute radial collapse probably occurred due to inflation at higher pressure with an oversized balloon, and relatively thin struts of the stent.

Nanocarriers are nanostructured vehicles employed to deliver anticancer drugs to the targeted tumor sites in the body. Nanocarriers have been successfully employed to circumvent certain limitations of conventional anticancer drug delivery while providing greater bioavailability, prolonged circulation time and higher tumor accumulation for enhanced therapeutic outcomes in cancer treatment. Nanocarriers are also responsive to functionalization to tailor their pharmaco-kinetics and achieve enhanced therapeutic outcomes in cancer therapy. Among organic, inorganic and hybrid type, several nanocarriers have gained approval for use in cancer patients, while many more are under clinical development. For the last two decades, cancer immunotherapy-based advanced targeting approaches such as monoclonal antibodies, antibody drug conjugates and immune checkpoint inhibitors that utilize human immune system functions have vastly developed which furnish better treatment options in several intractable cancers compared with traditional cancer therapies. This review discusses the imperative role of tumor vasculature in passive and active targeting of anticancer drugs using organic and inorganic nanocarriers and the current research efforts underway. The advanced targeting approaches for treatment of various cancers and their most recent clinical development scenario have been comprehensively explored. Further, potential challenges associated with each type of nanocarrier, and their translational obstacles are addressed.

Immune cells can actively regulate tumors or inflammatory sites and have good biocompatibility and safety. Currently, they are one of the most promising candidates for drug delivery systems. Moreover, immune cells can significantly extend the circulation time of nanoparticles and have broad-spectrum tumor-targeting properties. This article first introduces the immune cell types most commonly used in recent years, analyzes their advantages and disadvantages, and elucidates their application in anti-tumor therapy. Next, the various ways of loading nanoparticles on immune cells that have been used in recent years are summarized and simply divided into two categories: backpacks and Trojan horses. Finally, the two “mountains” that stand in front of us when using immune cells as cell carriers, off-target problems and effective release strategies, are discussed.

An abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta related to the regional weakening of the wall structure, resulting in substantial morbidity and mortality with the aortic ruptures as complications. Ruptured AAA is a dramatic catastrophe, and aortic emergencies constitute one of the leading causes of acute death in older adults. AAA management has been centered on surgical repair of larger aneurysms to mitigate the risks of rupture, and curative early diagnosis and effective pharmacological treatments for this condition are still lacking. Nanoscience provided a possibility of more targeted imaging and drug delivery system. Multifunctional nanoparticles (NPs) may be modified with ligands or biomembranes to target agents' delivery to the lesion site, thus reducing systemic toxicity. Furthermore, NPs can improve drug solubility, circulation time, bioavailability, and efficacy after systemic administration. The varied judiciously engineered nano-biomaterials can exist stably in the blood vessels for a long time without being taken up by cells. Here, in this review, we focused on the NP application in the imaging and treatment of AAA. We hope to make an overview of NP-assisted diagnoses and therapy in AAA and discussed the potential of NP-assisted treatment.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 seconds of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval:0.77-0.91), which means to have “Excellent reliability.” By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI), and New York Heart Association (NYHA) classification; 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N=28, ≥ or < 2.2 L/min/M2), 0.82 and 0.94 (NYHA Class I-II or Class III). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

Melanoma is a complex and highly aggressive skin tumor with increasing incidence worldwide. In this chapter, this malignant cancer is addressed, gathering information about epidemiology, mitochondrial role in the disease, clinical presentation, and therapeutic management. In the search for novel and more effective therapies against melanoma, pharmacologically active natural products have been explored, with several drugs reaching the market. In vitro and in vivo studies of natural compounds with potential antimelanoma activity are highlighted. Despite their promising potential, some of them can display unfavorable physicochemical and pharmacokinetic features that compromise their clinic translation. Over the last years, there have been advances in nanotechnology applied to cancer treatment that have overcome many of these limitations, providing versatile and effective tools for the successful in vivo delivery of natural molecules, namely lipid-based, polymeric, and metallic nanosystems. These nanocarriers allow not only the modulation of pharmacokinetic and pharmacodynamic profiles of the compounds, but also the increase of their stability and circulation time, resulting in greater therapeutic efficacy and less toxicity. Overall, this chapter focuses on nanoformulated natural-based compounds as an alternative therapeutic approach against melanoma, describing the most representative works from 2008 to 2020.

There is evolving evidence that bioactive peptides can be employed successfully to prevent and/or treat obesity. This chapter details the synthetic peptides currently employed as pharmaceutical treatments of obesity. It summarizes their efficacy, mode of action, circulation time, delivery route, and limitations. It also details peptidic drugs under development. Peptides derived from food have also been discovered that modulate appetite and/or reduce weight. This chapter focuses on their in vivo efficacy and the many challenges faced by food peptides or protein hydrolyzates to play a role in weight management.

During the last 20+ years, research into the biomedical application of nanotechnology has helped in reshaping cancer treatment. The clinical use of several passively targeted nanosystems resulted in improved quality of care for patients. However, the therapeutic efficacy of these systems is not superior to the original drugs. Moreover, despite extensive investigations into actively targeted nanocarriers, numerous barriers still remain before their successful clinical translation, including sufficient blood-stream circulation time and efficient tumor targeting. The combination of synthetic nanomaterials with biological elements (e.g., cells, cell membranes, and macromolecules) is presently the cutting-edge research in cancer nanotechnology. The features provided by the biological moieties render the particles with prolonged bloodstream circulation time and homotopic targeting to the tumor site. Moreover, cancer cell membranes serve as sources of neoantigens, useful in the formulation of nanovaccines. In this chapter, we will discuss the advantages of biohybrid nanosystems in cancer chemotherapy, immunotherapy, and combined therapy, as well as highlight their preparation methods and clinical translatability.

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Noninvasive treatments to treat the brain-related disorders have been paying more significant attention and it is an emerging topic. However, overcoming the blood brain barrier (BBB) is a key obstacle to most of the therapeutic drugs to enter into the brain tissue, which significantly results in lower accumulation of therapeutic drugs in the brain. Thus, administering the large quantity/doses of drugs raises more concerns of adverse side effects. Nanoparticle (NP)-mediated drug delivery systems are seen as potential means of enhancing drug transport across the BBB and to targeted brain tissue. These systems offer more accumulation of therapeutic drugs at the tumor site and prolong circulation time in the blood. In this review, we summarize the current knowledge and advancements on various nanoplatforms (NF) and discusses the use of nanoparticles for successful cross of BBB to treat the brain-related disorders such as brain tumors, Alzheimer’s disease, Parkinson’s disease, and stroke.

For the past few years, nanotechnology has provided a lot of new treatment opportunities for prostate cancer patients, and brilliant achievements have been acquired indeed. It not only prolonged circulation time in vivo but also increased bio-availability of drugs. Among them, nanoparticles with specificity ligand can be better targeted at prostate cancer, which improves the curative effect and reduces side effects. What's more, in terms of combined administration, the synergistic effect of chemotherapeutic drugs and hormones, or co-delivery two or more different drugs into the same delivery system, has achieved good therapeutic progress as well. In this paper, a comprehensive overview of nano-technology and the combination therapy for prostate cancer by pharmaceutical and clinical pharmaceutical strategies have been proposed to further appreciate and recommend the design and development of prostate cancer treatment.

Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to their translation. Successful clinical translation of these nanoparticles is heavily dependent on their stability, circulation time, access and bioavailability to disease sites, and their safety profile. This review covers preclinical and clinical inorganic-nanoparticle based nanomaterial utilized for cancer imaging and therapeutics. A special emphasis is put on the rational design to develop non-toxic/safe inorganic nanoparticle constructs to increase their viability as translatable nanomedicine for cancer therapies.

This study evaluated the safety, tolerability, and pharmacokinetics of a novel oral amphotericin B (AmB) formulation (iCo-019) following single doses to healthy humans. The data from this study suggest that iCo-019 has a long circulation time and systemic exposure without the associated gastrointestinal, liver, and kidney toxicity associated with AmB. This novel oral AmB formulation can serve as a new treatment strategy to overcome the limitations of the use of parenterally administered AmB products.

Increasing awareness of chronic pain due to both injury and disease have encouraged drug companies and pharmaceutical researchers alike to design and fabricate better, more specific drugs for pain relief. However, overuse of clinically available pain medication has caused a multitude of negative repercussions, including drug tolerance, addiction, and other severe side effects, which can prolong suffering and reduce pain mediation. Applications of nanotechnology to the field of drug delivery has sought to enhance the treatment efficiency, lower side effects, and mitigate the formation of tolerance. The use of nanomaterials has several advantages for chronic pain relief, such as controlled release, prolonged circulation time, and limited side effects. With the development of nanotechnology, strategies for chronic pain relief have also bourgeoned utilizing a variety of nanomaterials and targeting surface modifications. In addition to using these materials as carriers for drug delivery, nanomaterials can also be designed to have inherent properties that relieve chronic pain. This minireview covers the current status of designed nanomaterials for pain relief and provides a discussion of future considerations for nanotechnology designed for relieving chronic pain.

Exosomes are nano structured (50-90 nm) vesicles that originate from endosomal compartment of eukaryotic cells and are secreted into extracellular matrix. In recent years, there has been increased interest in exploring exosomes for diagnostic and therapeutic applications. Like many other diseases, e.g., neurodegenerative disorders, autoimmune diseases exosomes have a considerable significance in cancer too. Exosomes are known to prevail in large numbers and carry unique cargos in different types of cancers and thus are proving as versatile entities in understanding their biology of cancers and utilized as efficient diagnostic biomarkers in identification of cancer type. In addition to diagnostic applications, there has been an increased interest in recent years to exploit exosomes as carriers for delivery of therapeutic agents to target sites as well. This is indebted to their exceptional non-immunogenic and biomimetic properties that prompted researchers to use exosomes as carriers for delivery of therapeutic agents, e.g., drugs, genes and peptides. Exosomes also circumvent many drawbacks associated with other lipid or polymeric nanocarriers, e.g., low circulation time, lipid toxicities, long term stability, etc. However, in spite of many favorable aspects of exosome based therapy, there have been a number of challenges too. This review will focus on the current status of the exosome based drug therapy for cancer, the challenges faced and its potential for future clinical use.

Neurological diseases and injuries have profound impact on a patient's lifespan and functional capabilities, but often lack effective intervention strategies to address the underlying neuropathology. The blood–brain barrier is a major hurdle in the effective delivery of therapeutics to the brain. Recent discoveries in blood–brain barrier maintenance reveal a dynamic system where time of day, disease progression, and even biological variables all strongly influence its permeability and flux of molecules. Nanoparticles can be used to improve the efficacy of therapeutics by increasing circulation time, bioavailability, selectivity, and controlling the rate of payload release. Considering these recent findings, the next generation of pharmacological paradigms are evolving to leverage nanotechnology to turn therapeutic intervention to meet the needs of a specific patient (i.e. personalized medicine).

A 35-year-old male, a case of Takayasu arteritis on treatment with oral prednisolone and methotrexate, revealed novel ultrawide field fluorescein angiographic features in bilateral eyes. The typical features of delayed arm-retina circulation time, lobulated areas of nonperfusion in choroid, cattle trucking of red blood cells in veins, and delayed arteriovenous transit time were nicely captured. Additionally, we noted peripheral perivascular hyperfluorescence and disc hyperfluorescence. We believe these findings could possibly be used as markers of disease activity. Lack of marked capillary nonperfusion areas and marked perivascular leakage probably signifies modulation of disease activity by the immunosuppressants.

Nanotechnology has been extensively utilized in the design and development of powerful strategies for drug delivery and cancer theranostic. Nanoplatforms as a drug delivery system have many advantages such as in vivo imaging, combined drug delivery, extended circulation time, and systemic controlled release. The functional biomimetic drug delivery could be realized by incorporating stimuli-responsive (pH, temperature, redox potential, etc.) properties into the nanocarrier system, allowing them to bypass biological barriers and arrive at the targeted area. In this review, we discuss the role of internal stimuli-responsive nanocarrier system for imaging and drug delivery in cancer therapy. The development of internal stimuli-responsive nanoparticles is highlighted for precision drug delivery applications, with a particular focus on in vivo imaging, drug release performance, and therapeutic benefits.

Platelets, circulating blood cells derived from megakaryocytes, play a key role in various physical activities, including coagulation, hemostasis, the body's innate immune response, and cancer metastasis. By taking advantage of their key traits, researchers have developed strategies to exploit platelets and platelet-mimicking nanoassemblies to treat a number of conditions, including wounds, cancers, and bacterial infections. Compared to traditional polymer, lipsosome, and inorganic nanoparticles-based delivery systems, platelets and platelet-mimicking vehicles hold many advantages. Among these are their enhanced circulation time, their large volumes and surface areas for drug loading or conjugation, and their inherent ability to target some diseases. In this review, we will highlight the recent progress made in the development of disease-targeting platelets- and platelet-mimicking-vehicles as therapeutic platforms.

Exosomes are membrane-bound extracellular nanovesicles secreted by most cells and found in multiple sources, including bodily fluids, plants, fruit, and bovine milk. They play an important role as mediators of intercellular communication, having a distinct ability to carry small molecules, proteins, and nucleic acids to recipient cells over large distances. Moreover, competency in crossing usually poorly permeable biological barriers has led to their promising use in diagnostics and in therapeutics, either as therapeutic entities on their own or as drug delivery vehicles, with superior stability, biocompatibility, circulation time and target specificity in comparison to conventional drug delivery systems. The aim of this review is to summarise and critically discuss the current literature on the use of exosomes in a therapeutic setting, with a particular focus on their use as drug delivery vehicles for mucosal drug delivery.

Nanomedicine is an emerging field that combines knowledge of nanotechnology and material science with pharmaceutical and biomedical sciences, aiming to develop nanodrugs with increased efficacy and safety. Compared to conventional therapeutics, nanodrugs manifest higher stability and circulation time, reduced toxicity and improved targeted delivery. Despite the obvious benefit, the accumulation of imaging agents and nanocarriers in the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Numerous toxicology studies have demonstrated that exposure to nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications, representing a non-genotoxic mechanism of toxicant-induced health effects, are becoming recognized as playing a potential causative role in the aetiology of many diseases including cancer. This review i) provides an overview of recent advances in medical applications of NMs and ii) summarizes current evidence on their possible epigenetic toxicity. To discern potential health risks of NMs, since current data are mostly based upon in vitro and animal models, a better understanding of functional relationships between NM exposure, epigenetic deregulation and phenotype is required.

In vivo pretargeting stands as a promising approach to harnessing the exquisite tumor-targeting properties of antibodies for nuclear imaging and therapy while simultaneously skirting their pharmacokinetic limitations. The core premise of pretargeting lies in administering the targeting vector and radioisotope separately and having the 2 components combine within the body. In this manner, pretargeting strategies decrease the circulation time of the radioactivity, reduce the uptake of the radionuclide in healthy nontarget tissues, and facilitate the use of short-lived radionuclides that would otherwise be incompatible with antibody-based vectors. In this short review, we seek to provide a brief yet informative survey of the 4 preeminent mechanistic approaches to pretargeting, strategies predicated on streptavidin and biotin, bispecific antibodies, complementary oligonucleotides, and bioorthogonal click chemistry.

Water-sealed underground oil caverns are quite different from conventional underground projects because of the harsher conditions. For one of the largest such caverns in China, conventional grouting materials could not meet the project standard. Therefore, the authors invented a new grouting material based on sulfoaluminate cement (SAC) and studied its properties under pressure circulation. During circulation, the time to the hydration exothermic peak time was reduced, and the peak temperature increased with the pressure. The compressive strength decreased during circulation and with the circulation time. These results were important for grouting during the project.

Acute visual loss after facial injection of cosmetic materials is rarely reported. In this study, we report one patient who developed acute visual loss after an injection of botulinum toxin A for esthetic purposes. A 43-year-old Korean woman presented with a decrease in visual acuity to 20/800 after an injection of botulinum toxin A in the masseter muscle. The visual field testing showed an inferior altitudinal defect, and fluorescein angiography revealed a delayed arm-retinal circulation time. After intravenous and oral prednisolone was administered, the patient’s visual acuity gradually improved. Two months after the botulinum toxin A injection, the visual acuity had almost returned to baseline, with a remaining paracentral scotoma. This is the first case of acute visual loss following an injection of botulinum toxin A in a facial lesion. This case emphasizes that the potential risks of botulinum toxin A injection should be considered, and the procedure should be performed delicately.

An abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta that plagues millions. Its rupture incurs high mortality rates (~80-90%), pressing an urgent need for therapeutic methods to prevent this deadly outcome. Judiciously designed nanoparticles (NPs) have displayed a unique potential to fulfill this need. Aneurysms feature excessive inflammation and extracellular matrix (ECM) degradation. As such, typically inflammatory cells and exposed ECM proteins have been targeted with NPs for therapeutic, diagnostic, or theranostic purposes in experimental models. NPs have been used not only for encapsulation and delivery of drugs and biomolecules in preclinical tests, but also for enhanced imaging to monitor aneurysm progression in patients. Moreover, they can be readily modified with various molecules to improve lesion targeting, detectability, biocompatibility, and circulation time. This review updates on the progress, limitations, and prospects of NP applications in the context of AAA.

Pharmaceutical drugs can help eliminate tumors and prevent further disease spread. These drugs typically target and interrupt biological processes occurring in rapidly dividing cancerous cells. Unfortunately, many drug therapies (especially cytotoxic chemotherapeutics) are unable to discriminate between healthy and cancerous tissue, causing acute toxicity to healthy cells. To maximize therapeutic benefits and minimize side effects, new bioengineering strategies are required that can aid selective delivery of pharmaceuticals to target tissue. Here, we briefly describe anticancer pharmaceutical agents and discuss engineering approaches from the macro- to the nanoscale that help with the targeted delivery of these drugs. We focus on (1) strategies to increase the therapeutic yield and circulation time of pharmaceutical agents delivered across biological barriers; (2) design of continuous, controlled release systems to regulate drug delivery; and (3) examples of engineered targeted delivery strategies for site-specific therapeutic action.

Currently, despite many active compounds have been introduced to the treatment, cancer remains one of the most vital causes of mortality and reduced quality of life. Conventional cancer treatments may have undesirable consequences due to the continuous differentiating, dynamic and heterogeneous nature of cancer. Recent advances in the field of cancer treatment have promoted the development of several novel nanoformulations. Among them, the lipid coated nanosized drug delivery systems have gained an increasing attention by the researchers in this field owing to the attractive properties such as high stability and biocompatibility, prolonged circulation time, high drug loading capacity and superior in vivo efficacy. They possess the advantages of both the liposomes and polymeric nanoparticles which makes them a chosen one in the field of drug delivery and targeting. Core-shell type lipid-coated nanoparticle systems, which provide the most prominent advantages of both liposomes such as biocompatibility and polymeric/inorganic nanoparticles such as mechanic properties, offer a new approach to cancer treatment. This review discusses design and production procedures used to prepare lipid-coated nanoparticle drug delivery systems, their advantages and multifunctional role in cancer therapy and diagnosis, as well as the applications they have been used in.

To investigate time-dependent changes in oxygen saturation (SpO2) readings during fluorescein angiography (FA) or simultaneous fluorescein and indocyanine green angiography (F/I). A prospective observational study. One hundred twenty-five consecutive patients underwent FA or F/I. After application of the exclusion criteria, 67 patients (28 underwent FA, 39 underwent F/I) were included in the study. During angiography, SpO2 was measured by using a pulse oximeter and recording each second. The arm-to-retina circulation time (ARCT) was measured on the angiography video images. Latency time was defined as the time from intravenous injection of the dye to observation of a 3% decrease in the SpO2 reading, and variation SpO2, as the difference between baseline SpO2 and the lowest SpO2 value. The mean variation SpO2 was − 1.0 ± 0.6 during FA, and − 6.1 ± 1.5 during F/I. Variation SpO2 was within 2% during FA and > 3% during F/I. No corresponding changes were observed in the other vital signs or subjective symptoms. The mean latency time was 33.3 ± 6.4 s. Latency time was positively correlated with the ARCT in the F/I group (rs = 0.766, P

Fibrinolytic agents including plasmin and plasminogen activators improve outcomes in acute ischemic stroke and thrombosis by recanalizing occluded vessels. In the decades since their introduction into clinical practice, several limitations of have been identified in terms of both efficacy and bleeding risk associated with these agents. Engineered nanoparticles and microparticles address some of these limitations by improving circulation time, reducing inhibition and degradation in circulation, accelerating recanalization, improving targeting to thrombotic occlusions, and reducing off-target effects; however, many particle-based approaches have only been used in preclinical studies to date. This review covers four advances in coupling fibrinolytic agents with engineered particles: (a) modifications of plasminogen activators with macromolecules, (b) encapsulation of plasminogen activators and plasmin in polymer and liposomal particles, (c) triggered release of encapsulated fibrinolytic agents and mechanical disruption of clots with ultrasound, and (d) enhancing targeting with magnetic particles and magnetic fields. Technical challenges for the translation of these approaches to the clinic are discussed.

Drug nanoparticles hitchhike on erythrocytes to target chemotherapy to the lungs for treating metastasis., Despite being the mainstay of cancer treatment, chemotherapy has shown limited efficacy for the treatment of lung metastasis due to ineffective targeting and poor tumor accumulation. Here, we report a highly effective erythrocyte leveraged chemotherapy (ELeCt) platform, consisting of biodegradable drug nanoparticles assembled onto the surface of erythrocytes, to enable chemotherapy for lung metastasis treatment. The ELeCt platform significantly extended the circulation time of the drug nanoparticles and delivered 10-fold higher drug content to the lung compared with the free nanoparticles. In both the early- and late-stage melanoma lung metastasis models, the ELeCt platform enabled substantial inhibition of tumor growth that resulted in significant improvement of survival. Further, the ELeCt platform can be used to deliver numerous approved chemotherapeutic drugs. Together, the findings suggest that the ELeCt platform offers a versatile strategy to enable chemotherapy for effective lung metastasis treatment.

Advances in technology of the past decades led to development of new nanometer scale diagnosis and treatment approaches in cancer medicine leading to establishment of nanooncology. Inorganic and organic nanomaterials have been shown to improve bioimaging techniques and targeted drug delivery systems. Their favorable physico-chemical characteristics, like small sizes, large surface area compared to volume, specific structural characteristics, and possibility to attach different molecules on their surface transform them into excellent transport vehicles able to cross cell and/or tissue barriers, including the blood–brain barrier. The latter is one of the greatest challenges in diagnosis and treatment of brain cancers. Application of nanomaterials can prolong the circulation time of the drugs and contrasting agents in the brain, posing an excellent opportunity for advancing the treatment of the most aggressive form of the brain cancer—glioblastomas. However, possible unwanted side-effects and toxicity issues must be considered before final clinical translation of nanoparticles.

Cancer remains a global health problem largely due to a lack of effective therapies. Major cancer management strategies include chemotherapy, surgical resection, and radiation. Unfortunately, these strategies have a number of limitations, such as non-specific side effects, uneven delivery of the drugs, and lack of proper monitoring technology. Inorganic nanoparticles (NPs) are considered promising agents in treating and tracing cancer due to their unique physicochemical properties such as the controlled release of drugs, bioavailability, biocompatibility, stability, and large surface area. Also, they enhance the solubility of hydrophobic drugs, prolong their circulation time, prevent undesired off-targeting and subsequent side effects, making them efficient particles in cancer theranostics. Promising inorganic-NPs include gold, selenium, silica, and oxide NPs. Further, several techniques are used to modify the surface of inorganic-NPs, making them more efficient for the effective transport of therapeutic cargos to overcome cellular barriers. Thus, inorganic-NPs function effectively, surmounting the intrinsic drawbacks of traditional organic NPs. This mini-review summarizes the significant inorganic-NPs, their properties, surface modifications, cellular uptake, and bio-distributions, along with their potential use in cancer theranostics. We also discuss the promises and challenges faced during the inorganic-NPs mediated therapeutic approach for cancer and these particles' status in the clinical setting.

Atherosclerosis is one of the leading causes of mortality and morbidity worldwide. The consequences of atherosclerotic disease include chronic diseases, such as coronary artery disease and angina pectoris, and acute diseases like heart attacks and stroke. In the diagnosis and treatment of atherosclerosis, various nanotechnologies have been applied to enhance visualization of atherosclerotic lesions, improve target efficacy and extend circulation time. Among these nanotechnologies, micelles have been used widely because of their high encapsulation efficiency of drugs, convenient fabrication, prolonged retention time and good biocompatibility. Reviews devoted to introducing the application of micelles into the management of atherosclerosis have not been released to date. Therefore, in this review, we summarize the recent advances of micelles in the diagnosis and management of atherosclerosis and propose some suggestions and perspectives.

The rapid development of nanotechnology and optical imaging techniques provide the opportunity for visualizable monitoring the occurrence and progression of cancers with high efficiency and accuracy. Ideal platforms for sensing target analytes in vivo are characterized with good stability, biocompatibility, long-term circulation time and specific-cancer-targeting and tumor accumulation ability. By taking advantage of the versatile imaging modalities and intelligent nanoprobes, a variety of optical imaging strategies have been designed and constructed for sensitive and real-time imaging cancer biomarkers or tumor tissue in vivo. This review declares the design and fabrication of nanomaterial-based optical imaging platform and their applications in sensing and visualizing cellular cancer biomarkers and tumor microenvironments-related features in vivo. Special focus is to reveal the progresses of three optical modalities including fluorescence, photoacoustic imaging and surface enhanced Raman scattering for biomarkers imaging in vivo. We also outline the significant challenges and prospective of nanomaterial-based optical imaging towards cancer diagnosis and personalized medicine.

To achieve the best therapeutic efficacy and good prognosis, the drugs necessitate tailored profiles of excellent spatiotemporal control and therapeutic monitoring. Here we introduce a programmed theranostic nanoparticle with self-adapting properties for tumor-specific systemic treatment, including stealthy surface to prolong circulation time in blood, surface charge-reversion for tumor targeting, receptor-mediated internalization to increase intracellular accumulation, "proton sponge effect" for controllable drug release and escape from endo/lysosome. Encouragingly, in the process of drug-induced apoptosis, the therapeutic efficacy can be reported by fluorescence imaging in vivo, in situ and in real time. Therefore, this work provides a new paradigm for design of programmed theranositc nanomedicine and offers promising prospects for precise tumor treatment.

Minimizing the sequestration of nanomaterials (NMs) by the reticuloendothelial system (RES) can enhance the circulation time of NMs, and thus increase their tumor-specific accumulation. Liposomes are generally regarded as safe (GRAS) agents that can block the RES reversibly and temporarily. With the help of positron emission tomography (PET), we monitored the in vivo tissue distribution of 64Cu-labeled 40 × 10 nm gold nanorods (Au NRs) after pretreatment with liposomes. We systematically studied the effectiveness of liposome administration by comparing (1) differently charged liposomes; (2) different liposome doses; and (3) varying time intervals between liposome dose and NR dose. By pre-injecting 400 μmol/kg positively charged liposomes into mice 5 h before the Au NRs, the liver and spleen uptakes of Au NRs decreased by 30% and 53%, respectively. Significantly, U87MG tumor uptake of Au NRs increased from 11.5 ± 1.1 %ID/g to 16.1 ± 1.3 %ID/g at 27 h post-injection. Quantitative PET imaging is a valuable tool to understand the fate of NMs in vivo and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake.

International audience; Pluronics P94 are block-copolymer showing prolonged circulation time and tumor-cell internalization in vitro, suggesting a potential for tumor accumulation and as a drug carrier. Here we report the results of the radiolabeled-P94 unimers (P94-111 In-DTPA) on tumor uptake/ retention and biodistribution after intravenous and intratumoral injection to tumor-bearing mice. Intravenous administration results in a high radioactive signal in the liver; while in tumor and other healthy tissues only low levels of radioactivity could be measured. In contrast, the intratumoral injection of P94 resulted in elevated levels of radioactivity in the tumor and low levels in other organs, including the liver. Independently from the injection route, the tumor tissue presented long retention of radioactivity. The minimal involvement of off-target tissues of P94, together with the excellent tracer retention overtime in the tumor designates Pluronic P94 copolymer as a highly promising carrier for anti-tumor drugs.

The search for more efficient therapeutic strategies and diagnosis tools is a continuous challenge. Advances in understanding the biological mechanisms behind diseases and tissues regeneration have widened the field of applications of particulate systems. Particles are no more just protective systems for the encapsulated drugs, but they play an active role in the success of the therapy. Moreover, particles have been explored for innovative purposes as templates for cells growth and as diagnostic tools. Until few years ago the most relevant parameters in particles formulation were the chemistry and the size. Currently, it is known that other physical characteristics can remarkably affect the performance of particulate systems. Particles with non-conventional shapes exhibit advantages due to the increasing circulation time in blood stream, less clearance by the immune system and more efficient cell internalization and trafficking. Creation of compartments has been found useful to control drug release, to tune the transport of substances across biological barriers, to supply the target with more than one bioactive agent or even to act as theranostic systems. It is expected that such complex shaped and compartmentalized systems improve the therapeutic outcomes and also the patient's compliance, acting as advanced devices that serve for simultaneous diagnosis and treatment of the disease, combining agents of very different features, at the same time. In this review, we overview and analyse the most recent advances in particle shape and compartmentalization and applications of newly designed particulate systems in the biomedical field., Ana Catarina Lima acknowledges to the Portuguese Foundation for Science and Technology (FCT) for the PhD grant SFRH/BD/71395/2010. Work supported by MICINN (SAF2014-52632-R) Spain and FEDER, as well as by the FCT project PTDC/CTM-BIO/1814/2012.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Stroke is one of the leading causes of mortality and morbidity worldwide. Due to its poor prognosis, there is a major negative impact on the patients and their family's life quality. However, despite the severity of this pathology tissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke. Moreover, there is no effective treatment for hemorrhagic stroke and only some palliative procedures are often performed to improve the patient's quality of life. Considering this, nanotechnology can offer some advantages for the development of new therapies for stroke. Among the various types of nanomaterials, liposomes are the most extensively studied due to their biocompatibility, biodegradability, and low toxicity. Liposomes, as a drug delivery system, are able to mask therapeutic compounds and allow their passage through the blood-brain barrier. Liposomes also protect drugs from degradation in a biological environment, increasing the circulation time and accumulation in the target tissue. Hence, this review highlights the potential of liposomes applications for delivery of therapeutic compounds for treating stroke.