Ingrid Hilger

Ingrid Hilger
Friedrich Schiller University Hosptial Jena, Germany

Doctor of Philosophy

About

230
Publications
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Publications

Publications (230)
Article
Full-text available
Earlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target-specific protein expression, while almost ignoring effects related to the nanoparticle composition. Here, we demonstrate how the design and surface decoration of nanoparticles impact the p65 nuclear factor-kappa B (NF-κB) protein expression i...
Article
Full-text available
Purpose To investigate drug contamination of the working environment with paclitaxel drug-coated balloon (DCB) angioplasty due to loss of paclitaxel containing particles from the coating during DCB preparation, insertion, and inflation. Material and Methods In an experimetal laboratory setting, drug loss during removal of the protective cover and...
Article
Zusammenfassung Die optische Bildgebung spielte immer schon eine zentrale Rolle bei der Aufklärung von biologischen und physiologischen Mechanismen in der modernen Biologie und Medizin. Ausgehend von den guten Erfahrungen in der Lichtmikroskopie, hat man in jüngster Zeit anspruchsvolle meso- und makroskopische optische Bildgebungssysteme geschaffen...
Article
Full-text available
Ulcerative colitis is a disease that causes inflammation and ulcers in the colon and which is typically recurrent, and NF-κB proteins are important players during disease progression. Here, we assess the impact of silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against NF-κB p65 on a murine model of colitis. To this end, n...
Chapter
The use of heating in treating diseases is a rather old idea. In line with different technical developments in the last decades, different hyperthermia modalities have been raised for the treatment of tumors, which represent external heating sources of the human body. In the late 1950s, the idea of using iron oxide nanoparticles to be deposited in...
Article
Full-text available
Azide-terminated ultrasmall gold nanoparticles (2 nm gold core) were covalently functionalized with alkyne-terminated small-interfering siRNA duplexes by copper-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry). The nanoparticle core was visualized by transmission...
Article
Full-text available
In this study we looked for the main protein pathway regulators which were responsible for the therapeutic impact on colon cancers when combining magnetic hyperthermia with the chemotherapeutic agent 5-fluorouracil (5FU). To this end, chitosan-coated magnetic nanoparticles (MNP) functionalized with 5FU were intratumorally injected into subcutaneous...
Article
Full-text available
Magnetic nanoparticles have been investigated for microwave imaging over the last decade. The use of functionalized magnetic nanoparticles, which are able to accumulate selectively within tumorous tissue, can increase the diagnostic reliability. This paper deals with the detecting and imaging of magnetic nanoparticles by means of ultra-wideband mic...
Article
The transcription factor NF-κB and its signaling cascade both play key roles in all inflammatory processes. The most critical member of the NF-κB transcription factor family is p65. We investigated the role of cationic silica-coated calcium phosphate nanoparticles (spherical, diameter by SEM 50–60 nm; zeta potential about +26 mV; stabilized by poly...
Article
Full-text available
Heat has been used to treat tumors for thousands of years. There are reports of the Egyptians and Greek philosophers using such treatments as far back as 3000 BC and 500 BC respectively for various solid tumors. Albeit, in these cases, the treatment was not very controlled and consisted of hot sticks or blades placed against tissue in order to ther...
Article
Full-text available
Magnetic hyperthermia can cause localized thermal eradication of several solid cancers. However, a localized and homogenous deposition of high concentrations of magnetic nanomaterials into the tumor stroma and tumor cells is mostly required. Poorly responsive cancers such as the pancreatic adenocarcinomas are hallmarked by a rigid stroma and poor p...
Article
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Objective: Deep-tissue localization of thermal doses is a long-standing challenge in magnetic field hyperthermia (MFH), and remains a limitation of the clinical application of MFH to date. Here, we show that pulse sequencing of MFH leads to a more persistent inhibition of tumor growth and less systemic impact than continuous MFH, even when deliver...
Article
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Liposomes represent suitable tools for the diagnosis and treatment of a variety of diseases, including cancers. To study the role of the human epidermal growth factor receptor 2 (HER2) as target in cancer imaging and image-guided deliveries, liposomes were encapsulated with an intrinsically quenched concentration of a near-infrared fluorescent dye...
Article
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Magnetic nanoparticles (MNPs) have shown promising features to be utilized in combinatorial magnetic hyperthermia and chemotherapy. Here, we assessed if a thermo-chemotherapeutic approach consisting of the intratumoral application of functionalized chitosan-coated MNPs (CS-MNPs) with 5-fluorouracil (5FU) and magnetic hyperthermia prospectively impr...
Conference Paper
This contribution deals with the detection and imaging of magnetic modulated nanoparticles by means of ultra-wideband sensing. We performed phantom measurements in a practical measurement setup where the magnetic nanoparticles are modulated by a static and a low periodic changing external magnetic field. We investigated the influence of the modulat...
Article
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There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functio...
Article
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Liposomes are biocompatible nanocarriers with promising features for targeted delivery of contrast agents and drugs into the tumor microenvironment, for imaging and therapy purposes. Liposome-based simultaneous targeting of tumor associated fibroblast and the vasculature is promising, but the heterogeneity of tumors entails a thorough validation of...
Article
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Desmoplasia, an aberrant production of extracellular matrix (ECM), is considered as one predictive marker of malignancy of pancreatic cancer. In this paper, we study the effect of mild hyperthermia on fibrillary collagen architecture in murine Achilles tendons and in a pancreatic cancer model, in vitro, i.e. 3D hetero-type tumor spheroids, consisti...
Article
Full-text available
In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and that the coupling procedure did not alter the cytotoxic potential of the drugs. By treating tumor cells (BxPC3 and PANC-1) with the conjugated MNPs and magnetic hyperthermia (43...
Article
In the last three decades, many new cell‐penetrating peptides (CPPs) were developed that exhibited enhanced cell selectivity. Thus, we aimed to validate the tumor cell selectivity of peptides from this new generation, namely fragments mini‐crotamine and mini‐maurocalcine. Both of these peptides are derived from venoms. Furthermore, we studied an an...
Preprint
Doxorubicin (DOX) is a frequently used chemotherapeutic drug for breast cancer, but its site specificity and local internalization into tumor cells is rather low. In this paper we conjugated magnetic nanoparticles (MNPs) with DOX and/or a pseudopeptide NucAnt (N6L) as modality to enhance DOX-induced antitumor effects in breast cancer cells (BT474)....
Article
Full-text available
The underlying data demonstrates that the expression of endoglin in murine melanoma cells influences melanin production in the cells. Also, the data shows that melanin production is further increased when the cells are subcutaneously implanted in mice models and that the high melanin production prevents detection of the cells by fluorescence imagin...
Article
Full-text available
Background: Endoglin (CD105) is overexpressed on tumor cells and tumor vasculatures, making it a potential target for diagnostic imaging and therapy of different neoplasms. Therefore, studies on nanocarrier systems designed for endoglin-directed diagnostic and drug delivery purposes would expose the feasibility of targeting endoglin with therapeut...
Chapter
Optical Coherence Tomography (OCT) We describe the fundamental concept of optical coherence tomography (OCT) and discuss the two main working principles time domain OCT and frequency domain OCT. Then, we review extended functionalities including spectrally and polarization-resolved OCT as well as Doppler-OCT and show concepts for contrast enhanceme...
Data
The influence of pH and time (A) and the pH and temperature (B) onto the stability of MTX/MNPs. Notes: MTX/MNPs were incubated for the stated time under the corresponding conditions. 0 h: amount of MTX/MNP-bound MTX directly after coupling process (n≥3). Abbreviations: MNPs, magnetic nanoparticles; MTX, methotrexate.
Data
Microscopic (A) and macroscopic (B) MTX/MNP depositions in the tumor at 28 d after MTX/MNP application. Notes: (A) Hematoxylin and eosin staining of 3 µm tumor sections (FFPE) indicated diffuse and cytoplasmatic localization of intratumorally applied MTX/MNPs, allowing a repetition of AMF treatment. (B) Macroscopic depictions of the dissected tumor...
Article
Full-text available
Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation-or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To...
Article
Full-text available
Statement of significance: This work demonstrates the design of activatable bispecific liposomes aimed to target HER2, a poor prognosis tumor marker in many tumor types, and fibroblast activation protein (FAP), a universal tumor marker overexpressed on tumor fibroblasts and pericytes of almost all solid tumors. Encapsulating liposomes with a quenc...
Conference Paper
We present a breast phantom for experimental medical microwave imaging. The phantom structures separating the tissue mimicking liquids are 3D-printed based on conductive materials. The skin is cast by silicone composites with carbon powder and graphite. In comparison to 3D printing with common plastic, this approach allows the simulation of anatomi...
Article
Full-text available
So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic (EH, hot air) and intrinsic (MH, magnetic heating mediated by nanoparticles, MNP) heating induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC 3 cells). The impact of MH (100 µg M...
Article
Full-text available
Background Preclinical research implementing fluorescence-based approaches is inevitable for drug discovery and technology. For example, a variety of contrast agents developed for biomedical imaging are usually evaluated in cell systems and animal models based on their conjugation to fluorescent dyes. Biodistribution studies of excised organs are o...
Article
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The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood ve...
Article
The objective of this study was to determine an optimal dose of photodynamic therapy (PDT) for inducing apoptotic tumor cells in vivo. In this context, mice bearing human tongue-squamous epithelium carcinomas were treated with various photosensitizer concentrations and fluences. Tumor apoptosis was imaged after 2 days via a self-designed DY-734-ann...
Article
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In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actua...
Article
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Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess wh...
Article
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Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the pr...
Article
Mesoporous silica nanoparticles (MSNs) attract increasing interest in the field of gene and drug delivery due to their versatile features as a multifunctional drug delivery platform. Here, we describe poly(amidoamine) (PAMAM) dendron-functionalized MSNs that fulfill key prerequisites for a controllable intracellular drug release. In addition to hig...
Article
Full-text available
The treatment of tumors via hyperthermia has gained increased attention in the last years. Among the different modalities available so far, magnetic hyperthermia has the particular advantage of offering the possibility of depositing the heating source directly into the tumor. In this study, we summarized the present knowledge we gained on how to im...
Article
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Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEONLA-BSA, which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION s...
Article
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Au@Fe3O4 Janus particles (JPs) are heteroparticles with discrete domains defined by different materials. Their tunable composition and morphology confer multimodal and versatile capabilities for use as contrast agents and drug carriers in future medicine. Au@Fe3O4 JPs have colloidal properties and surface characteristics leading to interactions wit...
Article
Full-text available
Magnetic nanoparticles (MNPs) are used in different biomedical applications, whereby each application requires specific particle properties. To fulfill these requirements, particle properties have to be optimized by means of variation of crystal structure, particle size, and size distribution. To this aim, improved aqueous precipitation procedures...
Data
Correlation between side scatter measurements and SPION-loads. HUVECs were cultured for 48 hours in medium containing 0–100 µgFe/mL SPIONs. Notes: Relationship between the cellular SPION-load as measured by UVS (A) and MPS (B) and the normalized side scatter data delivered by flow cytometry. Results were acquired with SEONLA (left panel), SEONLA-BS...
Data
Biophysical properties of SPIONs. Notes: (A) Representative transmission electron micrographs of SEONLA-BSA, SEONLA and Rienso®. (B) Fourier transform infrared spectra of the nanoparticles. (C) Dynamic light scattering data of nanoparticles in water. (D) Zeta potential of investigated particles. (E–G) Biostability of nanoparticles. Nanoparticle sta...
Data
In vitro mCT imaging of AuroVist™ 1.9 nm and 15 nm after embedding in 1% agarose and after uptake into murine macrophages. Notes: (A) Ascending concentrations of AuroVist™ 1.9 nm and 15 nm NPs were embedded in 1% agarose (a), and contrast properties investigated via mCT (b). (B) Murine macrophages (J774A.1 cells) were co-incubated for 24 hours with...
Article
Full-text available
Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicabil...
Article
Full-text available
Due to their special physicochemical properties, iron nanoparticles offer new promising possibilities for biomedical applications. For bench to bedside translation of super-paramagnetic iron oxide nanoparticles (SPIONs), safety issues have to be comprehensively clarified. To understand concentration-dependent nanoparticle-mediated toxicity, the exa...
Article
Full-text available
Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial ce...
Article
Heterogeneous magnetic nanoparticle (MNP) distributions within tumors can cause regions of temperature under dosage and reduce the therapeutic efficiency. Here, micro-computed tomography (CT) imaging was used as a tool to determine the MNP distribution in vivo. The therapeutic success was evaluated based on tumor volume and temperature distribution...
Article
Aim Hyperthermia as cancer treatment is capable to induce cell death and consequently stop tumor growth. Tumor cells are specifically prone to hyperthermic temperatures; therefore, heat shock proteins (Hsp) like Hsp70 are expressed upon cellular stress. Here, an optical near-infrared (NIR) probe was developed to assess the therapeutic efficiency of...
Conference Paper
This paper presents a contrast enhancing approach for Ultra-wideband breast imaging by means of magnetic modulated iron oxide nanoparticles. The investigations are motivated by the low dielectric contrast between malignant and normal glandular/fibroconnective tissues in the breast. In this contribution two different modulation approaches are invest...
Data
High-resolution transmission electron microscopy (HRTEM) micrograph of 200 nm fluidMAG-D magnetic nanoparticles (MNP). Notes: HRTEM micrograph reveals smaller core particles of approximately 10–12 nm in size clustered to a particle core size of approximately 70 nm in total. The HRTEM micrograph was prepared as described elsewhere.37