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Nano-/microplastics (NP) is a human-made emerging contaminant with worldwide occurrence. The small size (below one micrometer), the different chemical nature and the persistence make NP to potential hazards with suspect probability of tissue penetration and inflammation or as accumulator for toxins. A strategy to stop the spill of novel NP is the remediation from waste water or rivers as prominent distributors. We have developed core–shell superparamagnetic iron oxide nanoparticles (SPIONs) that attract NP and glue them to larger agglomerates which then can be removed from water by applying an external magnetic field. The shell molecules provide two interaction motifs towards NP. The tuned surface potential of the functionalized SPIONs attract complementary charged NP efficiently and the n-alkyl chain is dedicated to preferential interaction towards organic NP rather than inorganic particles. Structural analytics and molecular dynamics simulation support the proposed concept. Systematic remediation experiments with different NP (chemical structures, sizes and mixtures), from different waters – including river water – and with different SPION core materials indicate a universal validity of the concept, with best remediation performance for mixed NP. We suggest a method for broadband remediation of various NP with simple materials and processes, which both have the potential to be up-scaled.

Peter Blümler,1 Ralf P Friedrich,2 Jorge Pereira,3 Olga Baun,1 Christoph Alexiou,2 Volker Mailänder3,4 1Institute of Physics, Johannes Gutenberg-University Mainz, Mainz, 55128, Germany; 2Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, 91054, Germany; 3Department of Physical Chemistry, Max Planck Institute for Polymer Research, Mainz, 55128, Germany; 4Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, GermanyCorrespondence: Peter BlümlerInstitute of Physics, Johannes Gutenberg-University Mainz, Staudingerweg 7, Mainz, 55128, GermanyTel +49 6131 3924240Fax +49 6131 3925179Email bluemler@uni-mainz.deAbstract: Controlled and contactless movements of magnetic nanoparticles are crucial for fundamental biotechnological and clinical research (eg, cell manipulation and sorting, hyperthermia, and magnetic drug targeting). However, the key technological question, how to generate suitable magnetic fields on various length scales (μm–m), is still unsolved. Here, we present a system of permanent magnets which allows for steering of iron oxide nanoparticles (SPIONs) on arbitrary trajectories observable by microscopy. The movement of the particles is simply controlled by an almost force-free rotation of cylindrical arrangements of permanent magnets. The same instrument can be used to move suspended cells loaded with SPIONs along with predetermined directions. Surprisingly, it also allows for controlled movements of intracellular compartments inside of individual cells. The exclusive use of permanent magnets simplifies scaled up versions for animals or even humans, which would open the door for remotely controlled in vivo guidance of nanoparticles or micro-robots.Keywords: permanent magnets, Halbach, super-paramagnetic, steering, targeting

Magnetic hybrid materials are a promising group of substances. Their interaction with matrices is challenging with regard to the underlying physical and chemical mechanisms. But thinking matrices as biological membranes or even structured cell layers they become interesting with regard to potential biomedical applications. Therefore, we established in vitro blood-organ barrier models to study the interaction and processing of superparamagnetic iron oxide nanoparticles (SPIONs) with these cellular structures in the presence of a magnetic field gradient. A one-cell-type–based blood-brain barrier model was used to investigate the attachment and uptake mechanisms of differentially charged magnetic hybrid materials. Inhibition of clathrin-dependent endocytosis and F-actin depolymerization led to a dramatic reduction of cellular uptake. Furthermore, the subsequent transportation of SPIONs through the barrier and the ability to detect these particles was of interest. Negatively charged SPIONs could be detected behind the barrier as well as in a reporter cell line. These observations could be confirmed with a two-cell-type–based blood-placenta barrier model. While positively charged SPIONs heavily interact with the apical cell layer, neutrally charged SPIONs showed a retarded interaction behavior. Behind the blood-placenta barrier, negatively charged SPIONs could be clearly detected. Finally, the transfer of the in vitro blood-placenta model in a microfluidic biochip allows the integration of shear stress into the system. Even without particle accumulation in a magnetic field gradient, the negatively charged SPIONs were detectable behind the barrier. In conclusion, in vitro blood-organ barrier models allow the broad investigation of magnetic hybrid materials with regard to biocompatibility, cell interaction, and transfer through cell layers on their way to biomedical application.

In the past decades, a wide variety of different superparamagnetic iron oxide nanoparticles (SPIONs) have been synthesized. Due to their unique properties, such as big surface-to-volume ratio, superparamagnetism and comparatively low toxicity, they are principally well suited for many different technical and biomedical applications. Meanwhile, there are a numerous synthesis methods for SPIONs, but high requirements for biocompatibility have so far delayed a successful translation into the clinic. Moreover, depending on the planned application, such as for imaging, magnetic drug targeting, hyperthermia or for hybrid materials intended for regenerative medicine, specific physicochemical and biological properties are inevitable. Since a summary of all existing SPION systems, their properties and application is far too extensive, this review reports on selected methods for SPION synthesis, their biocompatibility and biomedical applications.

Losing one's ability to speak, because of tissue deficiency at the vocal fold (VF), leads to serious impairment in the quality of life. Until now, there is no successful approach for regenerating the VF. The aim of this study was to show the advantage of magnetic nanoparticles in the generation of scaffold-free three-dimensional (3D) VF cell constructs by magnetic tissue engineering (MTE). Rabbit VF fibroblasts were used to establish MTE: after cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be controlled with a magnetic field thereby forming solid 3D cell structures. To transfer this method into human cells, SPIONs were adapted accordingly and tested for their influence on human VF (hVF) cells and for their ability to perform MTE with hVF cells. Of interest, the cell number and the magnet's shape influence the form of the rabbit VF cell construct. After successful characterization of hVF cells, biocompatibility analyses revealed no significant influence of SPIONs on them, thus 3D hVF cell constructs could be successfully generated by MTE. These basic results are important to develop MTE as an innovative method to regenerate functional VFs. We expect that in vivo studies, including MTE as an elegant, far-field controlled and touchless technology, will translate MTE VF bioconstructs into reconstructive laryngeal medicine. Impact Statement This study aims at nanotechnology for regenerative medicine by magnetic tissue engineering (MTE). New approaches for vocal fold (VF) reconstruction are desperately needed. Superparamagnetic iron oxide nanoparticles offer innovative, scaffold-free potentials for tissue engineering: MTE. By using MTE we could generate functional multilayered human VF cell constructs, which can consequently be used to regenerate the voice in patients with VF injuries.

According to the World Health Organization, cancer is the second most important cause of death in Europe. Due to its manifold manifestations, it is not possible to treat all patients according to a uniform scheme. However, all solid tumors have one thing in common: independent of the tumor’s molecular subgroup and the treatment protocol, the immune status of the tumor, especially the amount of tumor infiltrating lymphocytes (TILs), is important for the patient’s clinical outcome – the higher the number of TILs, the better the outcome. For this reason it seems desirable to increase the number of TILs. One way to accumulate T cells in the tumor area is to make them magnetizable and attract them with an external magnetic field. Magnetization can be achieved by superparamagnetic iron oxide nanoparticles (SPIONs) which can be bound to the cells’ surface or internalized into the cells. For this study, SPIONs with different coatings were synthesized and incubated with immortalized mouse T lymphocytes. SPIONs only stabilized with lauric acid (LA) coated in situ or afterwards showed high toxicity. Addition of an albumin layer increased the biocompatibility but reduced cellular uptake. To increase the cellular uptake the albumin coated particles were aminated, leading to both higher uptake and toxicity, dependent on the degree of amination. In the presence of an externally applied magnetic field, T cells loaded with selected types and amounts of SPIONs were guidable. With this promising pilot study we already can demonstrate that it is possible to attract SPION bearing T cells by an external magnet. To sum up, biocompatibility and uptake of SPIONs by T cells are opposing events. Thus, for the functionalization of T cells with SPIONs the balance between uptake and toxicity must be evaluated carefully.

Magnetic particle imaging (MPI) is a tomographic imaging method to determine the spatial distribution of magnetic nanoparticles (MNP) within a defined volume. To evaluate the imaging capabilities of existing MPI scanners, their sensitivity and image resolution limits have to be analyzed. Therefore, precisely defined structures (phantoms) with various tracer concentrations are required to enable comparative studies between existing MPI systems. To support the development of capable MPI phantoms, we developed a method to incorporate different commercially available MNP into a long-term stable synthetic polymer with an iron concentration of up to 200 mmol/l. The properties of each type of polymer matrix embedded MNP were tested by magnetic particle spectroscopy (MPS). For shaping the particle loaded polymer to a phantom, we used 3-D printed molds with a structure cross section of 2 × 2 mm2. The particle loads within the phantoms were then imaged using MPI. The particle-loaded polymer is very suitable for preparation of measurement phantoms that could be visualized by MPI. Repeated shore hardness and MPS measurements up to one year did not reveal any changes in the mechanical and magnetic properties of the used material. In conclusion, we developed long-term stable measurement phantoms for magnetic particle imaging. Further work will focus on more detailed particle loaded structures in phantoms and water based polymers with a more homogeneous particle distribution.

As emerging responsive materials, ferrogels have become highly attractive for biomedical and technical applications in terms of soft actuation, tissue engineering or controlled drug release. In the present study, bioderived ferrogels were fabricated and successfully deformed within moderate, heterogeneous magnetic fields. Synthesis was realized by arresting iron oxide nanoparticles in porcine gelatin by introduction of covalent crosslinks via treatment with energetic electrons for mesh refinement. This approach also allows for tuning thermal and mechanical stability of the gelatin matrix. Operating the bioferrogel in compression, magnetic forces on the nanoparticles are counterbalanced by the stiffness of the hydrogel matrix that is governed by a shift in thermodynamic equilibrium of swelling, as derived in the framework of osmosis. As gelatin and iron oxide nanoparticles are established as biocompatible constituents, these findings promise potential for in vivo use as contactless mechanical transducers.

Superparamagnetic iron oxide nanoparticles (SPIONs) feature distinct magnetic properties that make them useful and effective tools for various diagnostic, therapeutic and theranostic applications. In particular, their use in magnetic drug targeting (MDT) promises to be an effective approach for the treatment of various diseases such as cancer. At the cellular level, SPION uptake, along with SPION-mediated toxicity, represents the most important prerequisite for successful application. Thus, the present study determines SPION uptake, toxicity and biocompatibility in human head and neck tumor cell lines of the tongue, pharynx and salivary gland. Using magnetic susceptibility measurements, microscopy, atomic emission spectroscopy, flow cytometry, and plasma coagulation, we analyzed the magnetic properties, cellular uptake and biocompatibility of two different SPION types in the presence and absence of external magnetic fields. Incubation of cells with lauric acid and human serum albumin-coated nanoparticles (SPIONLA-HSA) resulted in substantial particle uptake with low cytotoxicity. In contrast, uptake of lauric acid-coated nanoparticles (SPIONLA) was substantially increased but accompanied by higher toxicity. The presence of an external magnetic field significantly increased cellular uptake of both particles, although cytotoxicity was not significantly increased in any of the cell lines. SPIONs coated with lauric acid and/or human serum albumin show different patterns of uptake and toxicity in response to an external magnetic field. Consequently, the results indicate the potential use of SPIONs as vehicles for MDT in head and neck cancer.

Background: The main goals of cancer treatment are not only to eradicate the tumor itself but also to elicit a specific immune response that overcomes the resistance of tumor cells against chemo- and radiotherapies. Hyperthermia was demonstrated to chemo- and radio-sensitize cancerous cells. Many reports have confirmed the immunostimulatory effect of such multi-modal routines. Methods: We evaluated the interaction of graphene oxide (GO) nanosheets, its derivatives reduced GO and PEGylated rGO, with components of peripheral blood and evaluated its thermal conductivity to induce cell death by localized hyperthermia. Results: We confirmed the sterility and biocompatibility of the graphene nanomaterials and demonstrated that hyperthermia applied alone or in the combination with radiotherapy induced much more cell death in tumor cells than irradiation alone. Cell death was confirmed by the release of lactate dehydrogenase from dead and dying tumor cells. Conclusion: Biocompatible GO and its derivatives can be successfully used in graphene-induced hyperthermia to elicit tumor cell death.

Cardiovascular diseases (CVD) account for nearly half of all deaths in Europe and almost 30% of global deaths. Despite the improved clinical management, cardiovascular mortality is predicted to rise in the next decades due to the increasing impact of aging, obesity, and diabetes. The goal of emerging cardiovascular nanomedicine is to reduce the burden of CVD using nanoscale medical products and devices. However, the development of novel multicom-ponent nano-sized products poses multiple technical, ethical, and regulatory challenges, which often obstruct their road to successful approval and use in clinical practice. This review discusses the rational design of nanoparticles, including safety considerations and regulatory issues, and highlights the steps needed to achieve efficient clinical translation of promising nanomedicinal products for cardiovascular applications.

A rational use of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, diagnostics, and other biomedical applications requires deep understanding of the molecular drug adsorption/desorption mechanisms for proper design of new pharmaceutical formulations. The adsorption and desorption of the cytostatic Mitoxantrone (MTO) to lauric acid-albumin hybrid coated particles SPIONs (SEONLA−HSA) was studied by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), surface titration, release experiments and small-angle neutron and X-ray scattering. Such MTO-loaded nanoparticles have shown very promising results in in vivo animal models before, while the exact binding mechanism of the drug was unknown. SEONLA−HSA formulations have shown better stability under drug loading in comparison with uncoated nanoparticle and sustainable drug release to compare with protein solution. Adsorption of MTO to SEONLA−HSA leads to decreasing of absolute value of zeta potential and repulsive interaction among particles, which points to the location of separate molecules of MTO on the outer surface of LA-HSA shell.

Conjugates based on nanostructured, superparamagnetic particles, a thermolabile linker and a cytotoxic maytansinoid were developed to serve as a model for tumour-selective drug delivery and release. It combines chemo- with thermal therapy. The linker-modified toxin was prepared by a combination of biotechnology and semisynthesis. Drug release was achieved by hyperthermia through an external oscillating electromagnetic field that induces heat inside the particles. Efficacy of this release concept was demonstrated both for cancer cell proliferation in vitro, and for tumour growth in vivo, in a xenograft mouse model. Biocompatibility studies for these magnetic-nanoparticle/ansamitocin conjugates complement this work.

Tissue-engineered scaffolds require an effective colonization with cells. Superparamagnetic iron oxide nanoparticles (SPIONs) can enhance cell adhesion to matrices by magnetic cell seeding. We investigated the possibility of improving cell attachment and growth on different alginate-based hydrogels using fibroblasts and endothelial cells (ECs) loaded with SPIONs. Hydrogels containing pure alginate (Alg), alginate dialdehyde crosslinked with gelatin (ADA-G) and Alg blended with G or silk fibroin (SF) were prepared. Endothelial cells and fibroblasts loaded with SPIONs were seeded and grown on hydrogels for up to 7 days, in the presence of magnetic field during the first 24 h. Cell morphology (fluorescent staining) and metabolic activity (WST-8 assay) of magnetically-seeded versus conventionally seeded cells were compared. Magnetic seeding of ECs improved their initial attachment and further growth on Alg/G hydrogel surfaces. However, we did not achieve an efficient and stable colonization of ADA-G films with ECs even with magnetic cell seeding. Fibroblast showed good initial colonization and growth on ADA-G and on Alg/SF. This effect was further significantly enhanced by magnetic cell seeding. On pure Alg, initial attachment and spreading of magnetically-seeded cells was dramatically improved compared to conventionally-seeded cells, but the effect was transient and diminished gradually with the cessation of magnetic force. Our results demonstrate that magnetic seeding improves the strength and uniformity of initial cell attachment to hydrogel surface in cell-specific manner, which may play a decisive role for the outcome in tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2948-2956, 2017.

Nearly one fourth of all deaths worldwide are attributable to cardiovascular diseases (CVD), including stroke and ischemic heart disease. In spite of the steady progress in cardiovascular diagnostics and therapy, the CVD prevalence continues to rise on a global scale. Persisting efforts in the fields of bio-engineering and tissue engineering, in parallel with improved understanding of disease mechanisms, have shifted the focus of research towards improved approaches to vascular regeneration, based on degradable biomaterials for temporary rather than permanent grafting. Utilizing advanced bioplotting techniques in order to combine cells, natural hydrogels and fibers, the production of tailored 3D vessel constructs that promote the regeneration of native tubular tissues has now become achievable. In this paper, we review the most promising biomaterials and additive manufacturing approaches to fabricate novel vascular constructs. In addition, we discuss the progress and the remaining challenges in the field.

Various nanoparticle systems have been developed for medical applications in recent years. For constant improvement of efficacy and safety of nanoparticles, a close interdisciplinary interplay between synthesis, physicochemical characterizations and toxicological investigations is urgently needed. Based on combined toxicological data, we follow a “safe-by design” strategy for our superparamagnetic iron oxide nanoparticles (SPION). Using complementary interference-free toxicological assay systems, we initially identified agglomeration tendencies in physiological fluids, strong uptake by cells and improvable biocompatibility of lauric acid (LA)-coated SPIONs (SPION LA ). Thus, we decided to further stabilize those particles by an artificial protein corona consisting of serum albumin. This approach finally lead to increased colloidal stability, augmented drug loading capacity and improved biocompatibility in previous in vitro assays. Here, we show in whole blood ex vivo and on isolated red blood cells (RBC) that a protein corona protects RBCs from hemolysis by SPIONs.

Superparamagnetische Eisenoxidnanopartikel (SPIONs) bieten vielfaltige Anwendungsmoglichkeiten in der Medizin. Toxikologische Untersuchungen, die auf der physikochemischen Charakterisierung der Nanopartikel aufbauen, sind eine wesentliche Voraussetzung fur die zukunftige Translation in die klinische Anwendung. Da Nanopartikel mit zahlreichen klassischen toxikologischen Nachweismethoden interferieren, sind Alternativmethoden notwendig. Multiparameterfarbungen fur Durchflusszytometrie und Fluoreszenzmikroskopie, markierungsfreie Echtzeitanalysen, 3D-Zellkultur und Flussmodelle werden diskutiert.

Magnetic hyperthermia is a technique that describes the heating of material through an external magnetic field. Classic hyperthermia is a medical condition where the human body overheats, being usually triggered by a heat stroke, which can lead to severe damage to organs and tissue due to the denaturation of cells. In modern medicine, hyperthermia can be deliberately induced to specified parts of the body to destroy malignant cells. Magnetic hyperthermia describes the way that this overheating is induced and it has the inherent advantage of being a minimal invasive method when compared to traditional surgery methods. This work presents a particle system that offers huge potential for hyperthermia treatments, given its good loss value, i.e., the particles dissipate a lot of heat to their surroundings when treated with an ac magnetic field. The measurements were performed in a low-cost custom hyperthermia setup. Additional toxicity assessments on Jurkat cells show a very low short-term toxicity on the particles and a moderate low toxicity after two days due to the prevalent health concerns towards nanoparticles in organisms.

Numerous medical applications make use of magnetic nanoparticles, which boosts the demand for imaging systems that can visualize these particles. Magnetomotive Ultrasound (MMUS) is an ultrasound-based imaging modality that can detect tissue perfused with magnetic nanoparticles. However, MMUS can only provide a qualitative mapping of the particle-loaded tissue. Therefore, we introduce in this contribution an extension of the MMUS algorithm that enables a quantitative representation of the nanoparticle density distribution in tissue. The presented algorithm is based on an iterative comparison between simulated data and measured data. Experiments with tissue-mimicking phantoms reveal that the presented procedure can be used to determine the local nanoparticle concentration in the correct order of magnitude.

Magnetic drug targeting utilizes an external magnetic field to target superparamagnetic iron oxide nanoparticles (SPIONs) and their cargo to the diseased vasculature regions. In the arteries, the flow conditions affect the behavior of magnetic particles and the efficacy of their accumulation. In order to estimate the magnetic capture of SPIONs in more physiological-like settings, we previously established an ex vivo model based on human umbilical cord arteries. The artery model was employed in our present studies in order to analyze the effects of the blood components on the efficacy of magnetic targeting, utilizing 2 types of SPIONs with different physicochemical characteristics. In the presence of freshly isolated human plasma or whole blood, a strong increase in iron content measured by AES was observed for both particle types along the artery wall, in parallel with clotting activation due to endogenous thrombin generation in plasma. Subsequent studies therefore utilized SPION suspensions in serum and washed red blood cells (RBCs) at hematocrit 50%. Interestingly, in contrast to cell culture medium suspensions, magnetic accumulation of circulating SPION-3 under the external magnet was achieved in the presence of RBCs. Taken together, our data shows that the presence of blood components affects, but does not prevent, the magnetic accumulation of circulating SPIONs.

The possibility to guide and control magnetic nanoparticles in a non-invasive manner has spawned various applications in biotechnology such as targeted drug delivery and sensing of biological substances. These applications are facilitated by the engineering of the size, selective chemical reactivity, and general chemical composition of the employed particles. Motivated by their widespread use and favorable properties, in this paper, we provide a theoretical study of the potential benefits of magnetic nanoparticles for the design of molecular communication systems. In particular, we consider magnetic nanoparticle based communication in a microfluidic channel where an external magnetic field is employed to attract the information-carrying particles to the receiver. We show that the particle transport affected by Brownian motion, fluid flow, and an external magnetic field can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are the particle size and the magnetic field gradient. Moreover, we derive an analytical expression for the channel impulse response, which is used to evaluate the potential gain in the expected number of observed nanoparticles due to the magnetic field. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles can enable reliable communication in the presence of disruptive fluid flow. Numerical results obtained by particle-based simulation validate the accuracy of the derived analytical expressions., Comment: 15 pages (double column), 8 figures, 1 table. Accepted for publication in the IEEE Transactions on NanoBioscience (TNB). (Author's comment: This is the extended journal version of the conference paper arXiv:1704.04206)

Design of functionalized biomimetic scaffolds is one of the key approaches for regenerative medicine and other biomedical applications. Development of engineered tissue should optimize organization and function of cells and tissue in vitro as well as in vivo. Surface topography is one factor controlling cellular behavior and tissue development. By topographical patterning of biocompatible materials, highly functionalized scaffolds can be developed. Gelatin is hereby a promising candidate due to its biocompatibility and biodegradability. It is low in cost and easy to handle, enabling a variety of applications in science and medicine. However, for biomedical applications at physiological conditions, gelatin has to be additionally stabilized since its gel-sol-transition temperature lies beneath the human body temperature. This is realized by a reagent-free cross-linking technique utilizing electron beam treatment. By topographical patterning, gelatin can be functionalized toward scaffolds for cell cultivation and tissue development. Thereby, customized patterns are transferred onto gelatin hydrogels via molds. Thermal stabilization of gelatin is then achieved by electron-induced cross-linking. In this study, we investigate the influence of gelatin concentration and irradiation dose on pattern transfer, long-term stability of topographically patterned gelatin hydrogels, and their impact on the cellular behavior of human umbilical vein endothelial cells as well as normal human dermal fibroblasts. We will show that contact guidance occurs for both cell types due to a concrete stripe pattern. In addition, the presented studies show a high degree of cytocompatibility, indicating a high potential of topographically patterned gelatin hydrogels as tissue development scaffold for prospective biomedical applications.

Molecular communication (MC) denotes information transmission by use of molecules and nanosized particles. For the realization of testbeds, superparamagnetic iron oxide nanoparticles (SPIONs) in duct flow have recently been proposed. Here, an experimental setup is provided to direct these particles at a branching of a tube into a specific direction by use of magnetic fields.

International audience; The objective of our work was to investigate the effects of different types of nanoparticles on endothelial (HUVEC) and monocytic cell functions. We prepared and tested 14 different nanosystems comprising liposomes, lipid nanoparticles, polymer, and iron oxide nanoparticles. Some of the tested nanosystems contained targeting, therapeutic, or contrast agent(s). The effect of particles (0-400 mu g/mL) on endothelial-monocytic cell interactions in response to TNF-alpha was investigated using an arterial bifurcation model and dynamic monocyte adhesion assay. Spontaneous HUVEC migration (0-100 mu g/mL nanoparticles) and chemotaxis of monocytic cells towards MCP-1 in presence of particles (0-400 mu g/mL) were determined using a barrier assay and a modified Boyden chamber assay, respectively. Lipid nanoparticles dose-dependently reduced monocytic cell chemotaxis and adhesion to activated HUVECs. Liposomal nanoparticles had little effect on cell migration, but one formulation induced monocytic cell recruitment by HUVECs under non-uniform shear stress by about 50%. Fucoidan-coated polymer nanoparticles (25-50 mu g/mL) inhibited HUVEC migration and monocytic cell chemotaxis, and had a suppressive effect on monocytic cell recruitment under non-uniform shear stress. No significant effects of iron oxide nanoparticles on monocytic cell recruitment were observed except lauric acid and human albumin-coated particles which increased endothelial-monocytic interactions by 60-70%. Some of the iron oxide nanoparticles inhibited HUVEC migration and monocytic cell chemotaxis. These nanoparticle-induced effects are of importance for vascular cell biology and function and must be considered before the potential clinical use of some of the analyzed nanosystems in cardiovascular applications.

Superparamagnetic iron oxide nanoparticles (SPIONs) have recently been introduced as information carriers in a testbed for molecular communication (MC) in duct flow. Here, a new receiver for this testbed is presented, based on the concept of a bridge circuit. The capability for a reliable transmission using the testbed and detection of the proposed receiver was evaluated by sending a text message and a 80 bit random sequence at a bit rate of 1/s, which resulted in a bit error rate of 0 %. Furthermore, the sensitivity of the device was assessed by a dilution series, which gave a limit for the detectability of peaks between 0.1 to 0.5 mg/mL. Compared to the commercial susceptometer that was previously used as receiver, the new detector provides an increased sampling rate of 100 samples/s and flexibility in the dimensions of the propagation channel. Furthermore, it allows to implement both single-ended and differential signaling in SPION-bases MC testbeds., Comment: ACM NanoCom 2019

The transfer of substances via the blood-placenta barrier is tightly regulated and critical for the fetus and the expecting mother. In case of necessary medical interventions during pregnancy a comprehensive knowledge about the interaction of the drugs with this barrier is indispensable. Therefore well-engineered test systems are needed and valuable transport systems are helpful. We developed an in vitro microfluidic blood-placenta barrier system consisting of the human trophoblast cell line BeWo and human primary placental pericytes. The integrity and stability of the model was verified by a permeability assay and immunocytochemistry. As potential drug carriers magnetic nanoparticles with various coatings were applied and their ability to pass the barrier was quantified by magnetic particle spectroscopy. We could demonstrate that up to 4% of negatively charged nanoparticles pass the barrier in a time-dependent manner.

Due to the presence of tripeptide arginine–glycine–aspartic acid, gelatin is considered a very promising additive material to improve the cytocompatibility of alginate-based hydrogels. Two different strategies, physical blending and chemical crosslinking with gelatin, are used in this study to modify alginate hydrogel. As the intermolecular interactions between the polysaccharide and protein in the resulting physically blended and chemically crosslinked hydrogels are different, significant differences in the properties of these hydrogel types, regarding especially their surface topography, degradation kinetics, mechanical properties, and protein release behavior, are observed. Cellular behavior on both types of alginate–gelatin hydrogels is investigated using primary human dermal fibroblasts to elucidate the effects of the different structural, mechanical, and degradation properties of the produced hydrogels on fibroblast attachment and growth. The hydrogel that is chemically crosslinked with gelatin exhibits the highest degree of cytocompatibility regarding adhesion, proliferation, metabolic activity, and morphology of growing fibroblasts.

In this work we present a new formulation of superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic drug targeting. The particles were reproducibly synthesized from current good manufacturing practice (cGMP) - grade substances. They were surface coated using fatty acids as anchoring molecules for human serum albumin. We comprehensively characterized the physicochemical core-shell structure of the particles using sophisticated methods. We investigated biocompatibility and cellular uptake of the particles using an established flow cytometric method in combination with microwave-plasma assisted atomic emission spectroscopy (MP-AES). The cytotoxic drug mitoxantrone was adsorbed on the protein shell and we showed that even in complex media it is slowly released with a close to zero order kinetics. We also describe an in vitro proof-of-concept assay in which we clearly showed that local enrichment of this SPION-drug conjugate with a magnet allows site-specific therapeutic effects.

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology.

Surface-functionalized gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) may be a useful tool in various biomedical applications. To obtain Au-SPIONs, gold salt was precipitated onto citrate-stabilized SPIONs (Cit-SPIONs) using a simple, aqueous one-pot technique inspired by the Turkevich method of gold nanoparticle synthesis. By the further stabilization of the Au-SPION surface with additional citrate (Cit-Au-SPIONs), controllable and reproducible Z-averages enhanced long-term dispersion stability and moderate dispersion pH values were achieved. The citrate concentration of the reaction solution and the gold/iron ratio was found to have a major influence on the particle characteristics. While the gold-coating reduced the saturation magnetization to 40.7% in comparison to pure Cit-SPIONs, the superparamagnetic behavior of Cit-Au-SPIONs was maintained. The formation of nanosized gold on the SPION surface was confirmed by X-ray diffraction measurements. Cit-Au-SPION concentrations of up to 100 &micro, g Fe/mL for 48 h had no cytotoxic effect on Jurkat cells. At a particle concentration of 100 &micro, g Fe/mL, Jurkat cells were found to take up Cit-Au-SPIONs after 24 h of incubation. A significantly higher attachment of thiol-containing L-cysteine to the particle surface was observed for Cit-Au-SPIONs (53%) in comparison to pure Cit-SPIONs (7%).

The availability of cell growth-supporting materials for regenerative medicine is limited. Here, we aimed to improve the attachment and growth of endothelial cells (HUVECs) and fibroblasts on electrospun poly(e-caprolactone) (PCL) mats with different fiber diameters and on newly-established PCL and silk fibroin (PCL/SF) blended fibers obtained by using benign solvents (mixture of acetic acid and formic acid) for electrospinning. PCL mats were produced in two different average fiber diameters, namely micro and nano range. The electrospinning method was optimized to produce PCL/SF blended fibers. Morphology (F-actin), viability (calcein) and metabolic activity (WST-8 assay) of HUVECs and fibroblasts cultured in 2D on the mats of different fiber size and composition were compared. Subsequently, cylindrical PCL/SF scaffolds were produced and colonized with cells using 3D radial magnetic cell seeding. Both PCL and PCL/SF nanofibers provided better support for initial cell adhesion (day 1) compared with PCL microfibers. At day 7, the highest metabolic activity in HUVECs and fibroblasts was observed on PCL/SF mats. Microscopic studies confirmed that on day 7, the best support for cell growth was observed on PCL/SF. Tubular PCL/SF scaffolds were successfully colonized using magnetic nanoparticles and 3D radial magnetic cell seeding. Taken together, the fibers obtained by blending SF with PCL combine the mechanical benefits of PCL with improved biological functionality of SF. Electrospun PCL/SF nanofibers represent a promising material to produce both flat and 3D structures with potential for enhanced cell attachment and tissue regeneration.

Metal-based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter. In this study, synchrotron radiation-based hard X-ray tomography (SRμCT) in absorption and phase contrast modes is evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X-ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model. This label-free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm-long animal with a spatial resolution of around 2 µm. High resolution image stacks are available on a dedicated internet page (http://zebrafish.pharma-te.ch). X-ray tomography is combined with physico-chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings. It is demonstrated that SRμCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of label-free metal oxide nanoparticles.

Systemic inflammation such as sepsis represents an acute life-threatening condition, to which often no timely remedy can be found. A promising strategy may be to functionalize magnetic nanoparticles with specific peptides, derived from the binding motives of agglutinating salivary proteins, that allow immobilization of pathogens. In this work, superparamagnetic iron oxide nanoparticles with stable polycondensed aminoalkylsilane layer were developed, to which the heterobifunctional linkers N-succinimidyl 3-(2-pyridyldithio)-propanoate (SDPD) and N-succinimidyl bromoacetate (SBA) were bound. These linkers were further chemoselectively reacted with the thiol group of singularly present cysteines of selected peptides. The resulting functional nanoparticles underwent a detailed physicochemical characterization. The biocompatibility of the primarily coated aminoalkylsilane particles was also investigated. To test the pathogen-binding efficacy of the particles, the lipopolysaccharide-immobilization capacity of the peptide-coated particles was compared with free peptides. Here, one particle-bound peptide species succeeded in capturing 90% of the toxin, whereas the degree of immobilization of the toxin with a system that varied in the sequence of the peptide dropped to 35%. With these promising results, we hope to develop extracorporeal magnetic clearance systems for removing pathogens from the human body in order to accelerate diagnosis and alleviate acute disease conditions such as sepsis.

Superparamagnetic iron oxide nanoparticles (SPIONs) are in use for many clinical diagnostic and experimental therapeutic applications, for example, for targeted drug delivery. To analyze the cellular responses to mitoxantrone-carrying SPIONs (SPION-MTO), and to the drug released from SPIONs, we used an in vitro system that allows comparison of primary human cells with different endocytotic capacities, namely, epithelial cells from proximal and distal parts of the nephron. SPIONs were selectively and rapidly internalized by proximal tubular cells with high endocytotic potential, but not by distal tubular cells. Uptake did not affect cell viability or morphology. In both cell types, free MTO (10–100 nM) induced double-strand DNA breaks and senescence, cell hypertrophy and reduced cell proliferation. However, cadherin-mediated cell–cell adhesion, cytoskeletal structures or polarity of the cells were not affected. Interestingly, a comparable response was also observed upon treatment with SPION-MTO and was independent of uptake of the particles. The effect of SPION-MTO on cells which did not internalize particles was primarily related to the release of MTO from drug-coated particles upon incubation in serum-containing cell growth medium. In conclusion, we show that whereas the uptake of SPIONs does not affect cellular functions or viability, the toxicity of drug-loaded SPIONs depends essentially on the type of drug bound to nanoparticles. Due to the relatively low systemic toxicity of MTO, the effects of MTO-SPIONs on human tubular cells were moderate, but they may become clinically relevant when more nephrotoxic drugs are bound to SPIONs.

Research in biomedical nanotechnology led already to a variety of applications of nanoparticles in diagnosis as well as in therapy. One of these medical applications is Magnetic Drug Targeting (MDT), a promising cancer treatment technique. The aim of this medical attendance is a local chemotherapeutic treatment of cancerous tissue. For this purpose, chemotherapeutic drugs are bound to magnetic nanoparticles and are, after injection, accumulated in the tumor area by means of an external static magnetic field. It has already been shown that magnetic nanoparticles can indirectly serve as ultrasound contrast agents, so sonographic technologies can be used as visualization technique for MDT. As nanoparticles are not visible directly using ultrasound imaging techniques because of their weak backscattering, the sonographic detection of nanoparticles in biological tissue has to be attributed to the detection of tissue movements, due to magnetically evoked nanoparticle movements. This type of sonographic detection is known as Magnetomotive Ultrasound (MMUS). In this context, a sinusoidal magnetic excitation signal is disadvantageous in terms of distinctness of particle induced movements, as respiratory movements or heartbeat movements may match the magnetic field frequency. Thus, in this contribution the use of coded magnetic excitation signals, which own a major recognition value, is investigated. Here, frequency coded signals are used as magnetic excitation signals, whereat the frequency modulation is carried out with a Barker sequence offering outstanding correlation properties. We show that coded magnetic fields enable the detection of magnetic nanoparticles even if further tissue movements are superposed.

A series of monomethine, trimethine- and styrylcyanine dyes based on a [1,10]phenanthroline moiety was synthesized, characterized and investigated as potential fluorescent probes for nucleic acids in cell free settings and in cells. The dyes were found to be weakly fluorescent in the unbound state, whereas upon the binding to dsDNA or RNA their emission intensity raised up to 50 times (for monomethine benzothiazole derivative FT1 complexed with RNA). The strongest fluorescence intensity in assemblies with dsDNA and RNA was observed for the trimethine benzothiazole derivative FT4. The quantum yield of FT4 fluorescence in its complex with dsDNA was found to be 1.5% and the binding constant (K b) was estimated to be 7.9 × 104 M-1 that is a typical value for intercalating molecules. The FT4 dye was found to be cell membrane permeable. It stains RNA rich components-the nucleoli and most probably the cytoplasmic RNA. FT4 bound to RNAs delivers a very strong fluorescence signal, which makes this easily accessible dye a potentially useful alternative to known RNA stains, e.g. expensive SYTO® 83. The advantage of FT4 is its easy synthetic access including no chromatographic purification steps, which will be reflected in its substantially lower price.

In this paper, we propose to use magnetic nanoparticles as information carriers for molecular communication. This enables the use of an external magnetic field to guide information-carrying particles towards the receiver. We show that the particle movement can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are particle size and magnetic field gradient. As an example, we consider magnetic nanoparticle based communication in a bounded two-dimensional environment. For this model, we derive an analytical expression for the channel impulse response subject to fluid flow and magnetic drift. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles facilitates reliable communication, even in the presence of fluid flow., 6 pages, 4 figures, 1 table. Submitted to the IEEE Wireless Communications and Networking Conference (IEEE WCNC) 2018. Changes: Clarified two-dimensional environment

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic., This work was supported by the Deutscher Akademischer Austauschdienst (DAAD to Philipps Universität Marburg and Zhejiang University, Hangzhou), the Chinesisch Deutsches Zentrum für Wissenschaftsförderung (“CDZ” to Z.G. and W.J.P.), and the Chinese Academy of Science (CAS). Part of this work was supported by the National Natural Science Foundation (51390481, 81227902, 81625011), National Basic Research Program (2014CB931900) of China (to Y.S.), by the European Commission grant Futurenanoneeds (to V.P. and W.J.P.), by the Spanish Ministerio de Economia y Competitividad (CTQ2011-23167 and CTQ2014-59808R to R.A.A.P.), the Generalitat of Catalunya (2014-SGR-612 to R.A.A.P.), the Deutsche Forschungsgemeinschaft (DFG) (AL552/8-1 to R.T.), the Swiss National Science Foundation (NRP62 to P.H.), the Claude & Julianna Foundation (grant to P.H.), the National Science Foundation (NSF) grants CHE-1306928 (to R.P.) and ECS-0601345; CBET 0933384; CBET 0932823; and CBET 1036672 (to N.A.K.), Canadian Institute of Health Research (grant to W.C.W.C.), and Natural Sciences and Engineering Research Council of Canada (grant to W.C.W.C.). S.A. and B.P. acknowledge a fellowship from the Alexander von Humboldt Foundation. N.F. acknowledges the Lars Hiertas Minne Foundation. M.C. acknowledges Ikerbasque for a Research Fellow position. X.C. acknowledges the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). B.Z.T. acknowledges the Innovation and Technology Commission of Hong Kong (ITC-CNERC14SC01). The Pancreatic Cancer research of A.E.N. and H.M. was funded by the U.S. National Cancer Institute, NIH grant # U01CA198846. A.E. acknowledges Junta de Andalucía (Spain) for a Talentia Postdoc Fellowship, co-financed by the European Union's Seventh Framework Programme, grant agreement no 267226. A.G.S. acknowledges support by BOF (UGent) and FWO (Research Foundation Flanders). Part of this work was supported by the National Natural Science Foundation of China.

Research in biomedical nanotechnology led already to a variety of applications of nanoparticles in diagnosis as well as in therapy. One of these medical applications is Magnetic Drug Targeting (MDT), a promising cancer treatment technique. The aim of this medical attendance is a local chemotherapeutic treatment of cancerous tissue. For this purpose, chemotherapeutic drugs are bound to magnetic nanoparticles and are accumulated in the tumor area by means of an external static magnetic field. It has already been shown that magnetic nanoparticles can indirectly serve as ultrasound contrast agents, so sonographic technologies can be used as visualization technique for MDT. As nanoparticles are not visible directly using ultrasound imaging techniques because of their weak backscattering, the sonographic detection of nanoparticles in biological tissue has to be attributed to the detection of tissue movements, due to magnetically evoked nanoparticle movements. This type of sonographic detection is known as Magnetomotive Ultrasound (MMUS). In this connection, a sinusoidal magnetic excitation signal is disadvantageous in terms of distinctness of particle induced movements, as respiratory movements or heartbeat movements may match the magnetic field frequency. Thus, in this contribution the use of coded magnetic excitation signals, which own a major recognition value, is investigated. A frequency coded linear up-chirp signal is used as magnetic excitation signal and is decoded from the collected rf-data employing the Fractional Fourier Transform (FrFT), which is a generalization of the classical Fourier Transform and which is appropriate for detecting frequency modulated signals. In this contribution we show a special algorithm based on the principle of MMUS that allows to detect the nanoparticle loaded tissue and which reduces the risk of misleading interpretation of particle loaded tissue due to naturally occuring tissue movements.

Functionalized superparamagnetic iron oxide nanoparticles are frequently used to develop vehicles for drug delivery, hyperthermia, and photodynamic therapy and as tools used for magnetic separation and purification of proteins or for biomolecular imaging. Depending on the application, there are various possible covalent and non-covalent approaches for the functionalization of particles, each of them shows different advantages and disadvantages for drug release and activity at the desired location. Particularly important for the production of adsorptive and covalent bound drugs to nanoparticles is the pureness of the involved formulation. Especially the covalent binding strategy demands defined chemistry of the drug, which is stabilized by excess free amino acids which could reduce reaction efficiency. In this study, we therefore used tangential flow filtration (TFF) method to purify the drugs before the reaction and used the frequently applied and clinically available recombinant tissue plasminogen activator (tPA; Actilyse®) as a proof of concept. We then coupled the tPA preparation to polyacrylic acid-co-maleic acid (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) using an amino-reactive activated ester reaction and compared these particles to PAM-coated SPIONs with electrostatically adsorbed tPA. Using dynamic light scattering (DLS) and pH-dependent electrokinetic mobility measurements, we showed that surface properties of the SPIONs were significantly greater affected after activation of the particles compared to the adsorption controls. Different in vitro assays were used to investigate the activity of tPA after coupling to the particles and purification of the ferrofluid. Covalent linkage significantly improves the reactivity and long-term stability of the conjugated SPION-tPA system compared to simple adsorption. In conclusion, we have shown an effective way to produce SPIONs with covalent and non-covalent ultra-filtrated drugs. We showed that using activated ester reaction, immobilization of the protein was significantly better than in adsorptive approaches. Investigation of those functionalized SPIONs revealed diverging attributes, which should be taken into account when developing nanoparticles for different applications. Electronic supplementary material The online version of this article (doi:10.1186/s11671-016-1521-7) contains supplementary material, which is available to authorized users.

Multifunctional GM1–modified lipoprotein-like nanoparticles for the therapy of Alzheimer’s Disease Evaluation of: Huang M, Hu M, Song Q et al. GM1–modified lipoproteinlike nanoparticle: multifunctional nanoplatform for the combination therapy of Alzheimer’s disease. ACS Nano. 9(11), 10801–10816 (2015). Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting about 11% of people aged 65 years and older in the USA alone. According to the estimates, this number may nearly triple by 2050 [1] resulting in an increased health and economic burden, which urgently calls for more effective therapies. The molecular basis for the formation of the extracellular amyloid plaques found in the brain of AD patients involves the strong neurotoxic effects of soluble amyloid-β (Aβ) [2]. In their recent paper, Huang et al. have developed a flexible multifunctional noninvasive drug delivery system for accelerated Aβ clearance, protection of neurons and inhibition of other pathological cascades induced by Aβ accumulation. Reconstituted high-density lipoprotein (rHDL) and monosialotetrahexosylganglioside (GM1)-rHDL nanoparticles were prepared by self-assembly from lipid-free apoE3 and 1,2–dimyristoyl-sn-glycero–3–phosphocholine (DMPC) liposomes or GM1–DMPC liposomes, respectively [3]. Surface plasmon resonance analysis showed a very high affinity of GM1–rHDL to monomeric and oligomeric Aβ 1–42 , comparable with anti-Aβ antibody binding. Following the extensive physicochemical analyses, in vivo experiments demonstrated a high level of GM1–rHDL in the brain after intranasal application in mice, confirming the feasibility of noninvasive administration of these nanoparticles. Subsequent in vitro and in vivo experiments revealed a strong improvement of different Aβ clearing pathways in the presence of GM1– rHDL as compared with rHDL. In primary microglia, GM1–rHDL facilitated the cellular uptake and intracellular degradation of Aβ 1–42 . Increased Aβ degradation and an accelerated Aβ brain-to-blood efflux after injection of I-labeled Aβ 1–42 oligomers into the unilateral hippocampus was also achieved in vivo with intranasally administered GM1–rHDL. Beside increased Aβ levels, AD is characterized by loss of neurons and synapses leading to memory loss, cognitive deficits and ultimately to death. Consequently, a successful therapy should combine strategies for Aβ clearance and neuroprotection. To verify the drugdelivery capacity of GM1–rHDL, the authors selected a neuroprotective octapeptide, NAP, as a model drug for AD. The resulting αNAP-GM1–rHDL particles increased the viability of Aβ 1–42 oligomer-treated primary neurons and reversed neuronal dysfunction by increasing the neurite length and branch point counts. Additionally, αNAP-GM1–rHDL Novel nanoparticulate drug delivery systems

Aim: We report the physicochemical analysis of nanosystems intended for cardiovascular applications and their toxicological characterization in static and dynamic cell culture conditions. Methods: Size, polydispersity and ζ-potential were determined in 10 nanoparticle systems including liposomes, lipid nanoparticles, polymeric and iron oxide nanoparticles. Nanoparticle effects on primary human endothelial cell viability were monitored using real-time cell analysis and live-cell microscopy in static conditions, and in a flow model of arterial bifurcations. Results & conclusions: The majority of tested nanosystems were well tolerated by endothelial cells up to the concentration of 100 μg/ml in static, and up to 400 μg/ml in dynamic conditions. Pilot experiments in a pig model showed that intravenous administration of liposomal nanoparticles did not evoke the hypersensitivity reaction. These findings are of importance for future clinical use of nanosystems intended for intravascular applications.

Cardiovascular diseases, including ischemic heart disease and stroke, are responsible for nearly 25% of all deaths worldwide. Globally, their prevalence continues to increase, in spite of enormous progress in cardiovascular diagnostics and therapy. For therapeutic and regenerative purposes, biomaterials promise solutions with multiple advantages over synthetic materials. Furthermore, their easy availability as nanoformulations recommends their application as drug carriers or protective nanoshells improving the biocompatibility of imaging agents. In this work, we review the most promising and clinically meaningful scientific reports with regard to (nano)biomaterials with particular focus on potential improvements of existing, and development of novel constructs for cardiovascular applications.