Robert Nissler

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Nissler

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Robert

ORCID

0000-0003-1282-2901

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Publications 1 - 8 of 8

Bioglass/Ceria Nanoparticle Hybrids for the Prophylactic Treatment of Seroma: A Comparative Short-Term Study in Rats
Pais, Michael-Alexander; de Brot, Simone; Nissler, Robert; et al. (2025)
ACS Pharmacology & Translational Science
Seroma formation remains a common postoperative complication. While optimal treatment remains unclear, recent attention has turned to bioglass/ceria nanoparticle (NP) treatment for seromas. Previous work showed complete seroma resolution in a rat model after NP treatment in the long term. This study aimed to assess the short-term prophylactic effects of NPs. Twenty male Lewis rats underwent bilateral seroma induction surgery. Postoperatively, seroma cavities were treated with NPs, vehicle buffer solution, or fibrin glue or left untreated. Over 2 weeks, blood, seroma fluid, and tissues were collected for biochemical, histopathological, and immunohistochemical analyses. By day 14, NP-treated seromas showed 100% fluid resolution. In contrast, seromas persisted in 50% of fibrin glue–treated rats, 60% of vehicle-treated rats, and 44.44% of untreated controls. Furthermore, prophylactic NP treatment resulted in decreased levels of inflammatory markers while the effect of fibrin glue was to increase the pro-inflammatory response. Histologically, a reduction in vascularization and individual macrophage infiltration was observed in seroma superficial capsules after NP treatment, while complement proteins were significantly increased and associated with groups of macrophages that colocalized with NPs. At the end point, NPs did not show any biodistribution to the systemic circulation. Prophylactic NP application reduced early seroma manifestations mostly through their anti-inflammatory effects. Members of the complement cascade were also identified in macrophages that colocalized with NPs and were internalized. Moreover, there were no detectable adverse systemic effects. These findings emphasize the clinical potential of NPs in the prevention of seromas and their potential for clinical use.
Bioglass/ceria nanoparticle hybrids for the treatment of seroma: a comparative long-term study in rats
Pais, Michael-Alexander; Papanikolaou, Athanasios; Hoyos, Isabel Arenas; et al. (2024)
Frontiers in Bioengineering and Biotechnology
Background: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism.Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made.Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides.Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy.
Protein Aggregation on Metal Oxides Governs Catalytic Activity and Cellular Uptake
Nissler, Robert; Dennebouy, Lena; Gogos, Alexander; et al. (2024)
Small
Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano-analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue-resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments.
An Augmented Reality Visor for Intraoperative Visualization, Guidance, and Temperature Monitoring Using Fluorescence
Cipolato, Oscar; Fauconneau, Matthias; LeValley, Paige J.; et al. (2025)
Journal of Biophotonics
Fluorescence-guided surgeries, including tumor resection and tissue soldering, are advancing the frontiers of surgical precision by offering enhanced control that minimizes tissue damage, improving recovery and outcomes. However, integrating fluorescence visualization with real-time temperature monitoring remains a challenge, limiting broader clinical use. We address this issue with an augmented reality (AR) visor that combines nanomaterial excitation, fluorescence detection, and temperature monitoring. Using advanced fluorescent nanoparticles like indocyanine green-doped particles and carbon nanotubes, the visor provides a comprehensive view of both the surgical field and sub-surface conditions invisible to the naked eye. This integration improves the safety and efficacy of fluorescence-guided surgeries, including laser tissue soldering, by ensuring optimal temperatures and laser guidance in real time. The presented technology enhances existing surgical techniques and supports the development of new strategies and sensing technologies in areas where traditional methods fall short, marking significant progress in precision surgery and potentially improving patient care.
Responsive Mn-Ferrite Nanoparticles for Multicolor Magnetic Particle Imaging, Sensing, and Reactive Oxygen Species Degradation
Starsich, Fabian H.L.; Feye, Julia; Nissler, Robert; et al. (2025)
Advanced Sensor Research
New possibilities offered by Magnetic Particle Spectroscopy (MPS) and Imaging (MPI) are increasingly being recognized and may accelerate the introduction of MPI into clinical settings. As MPI is a tracer-based imaging method, the design and development of responsive tracers for functional imaging are particularly appealing. Here, Mn-ferrite (Mn$_x$Fe$_{3-x}$O$_4$) nanoparticles with finely tuned magnetic properties and enzyme-like capabilities are reported as potential multifunctional theranostic agents. By adjusting the Mn content in the iron oxide matrix, the magnetic particle imaging signal of different tracers can be tweaked, allowing for the simultaneous quantitative detection of two different tracers in a multi-color approach. The Mn$_2$FeO$_4$ tracers exhibit potent enzyme-like catalytic properties, enabling degradation of reactive oxygen species, including H$_2$O$_2$ and OH$^-$. Due to the readily interchangeable oxidation states of Mn and Fe atoms in the crystal structure, a strong dependence of the magnetic properties is observed on H$_2$O$_2$ exposure, which can be exploited for sensing. This enables, for the first time, the sensing of reactive oxygen species based on magnetic particle spectroscopy and imaging, with sensitivity down to 25 μm H$_2$O$_2$ and complete sensor recovery over time. In summary, Mn-ferrite nanoparticles hold promising potential for imaging, sensing, and degradation of disease-relevant reactive oxygen species.
Unlocking NIR-II Photoluminescence in 2D Copper Tetrasilicate Nanosheets through Flame Spray Synthesis
Nissler, Robert; Zhou, Quanyu; Hill, Björn; et al. (2025)
Advanced Materials
Expanding fluorescence bioimaging into the second near-infrared spectrum (NIR-II, 1000-1700 nm) unlocks advanced possibilities for diagnostics and therapeutics, offering superior tissue penetration and resolution. 2D copper tetrasilicate (CTS) pigments (MCuSi₄O₁₀, M = Ca, Sr, Ba) are known for their brightness and stability, yet synthetic challenges have curbed their integration into bioimaging. Here, flame-spray-pyrolysis (FSP) is introduced as a versatile and scalable synthesis approach to produce ultra-bright, metastable CTS nanosheets (NS) by annealing multi-element metal oxide nanoparticles into 2D crystals through calcination or laser irradiation. Group-II ion incorporation shifts emission into the NIR-II range, with Ba_(0.33)Sr_(0.33)Ca_(0.33)CuSi₄O₁₀ peaking at 1007 nm, while minor Mg-doping induces a hypsochromic shift and extends fluorescence lifetimes. The engineered CTS achieves quantum yields of up to 34%, supporting NS high-frame-rate imaging (> 200 fps). These unique properties enable CTS-NS to serve as powerful contrast agents for super-resolution NIR bioimaging, demonstrated in vivo through transcranial microcirculation mapping and macrophage tracking in mice using diffuse optical localization imaging (DOLI). This pioneering synthesis strategy unlocks wavelength-tunable NS for advanced NIR-II bioimaging applications.
Material-Intrinsic NIR-Fluorescence Enables Image-Guided Surgery for Ceramic Fracture Removal
Nissler, Robert; Totter, Elena; Walter, Sebastian G.; et al. (2024)
Advanced Healthcare Materials
Hip arthroplasty effectively treats advanced osteoarthritis and is therefore entitled as "operation of the 20th century." With demographic shifts, the USA alone is projected to perform up to 850 000 arthroplasties annually by 2030. Many implants now feature a ceramic head, valued for strength and wear resistance. Nonetheless, a fraction, up to 0.03% may fracture during their lifespan, demanding complex removal procedures. To address this, a radiation-free, fluorescence-based image-guided surgical technique is presented. The method uses the inherent fluorescence of ceramic implant materials, demonstrated through chemical and optical analysis of prevalent implant types. Specifically, Biolox delta implants exhibited strong fluorescence around 700 nm with a 74% photoluminescence quantum yield. Emission tails are identified extending into the near-infrared (NIR-I) biological transparency range, forming a vital prerequisite for the label-free visualization of fragments. This ruby-like fluorescence could be attributed to Cr within the zirconia-toughened alumina matrix, enabling the detection of even deep-seated millimeter-sized fragments via camera-assisted techniques. Additionally, fluorescence microscopy allowed detection of mu m-sized ceramic particles, enabling debris visualization in synovial fluid as well as histological samples. This label-free optical imaging approach employs readily accessible equipment and can seamlessly transition to clinical settings without significant regulatory barriers, thereby enhancing the safety, efficiency, and minimally invasive nature of fractured ceramic implant removal procedures.
Chemical vs Physical Radioenhancement from TiO₂and Au Nanoparticles to Overcome Hypoxic Radioresistance in X-ray Therapy
Gerken, Lukas; Schaller, Laurin G.S.; Nissler, Robert; et al. (2025)
Nano Letters
Hypoxia, a common feature in solid tumors, induces cellular radioresistance and reduces radiotherapy efficacy. Nanoparticles present a promising radiosensitizing approach providing localized dose enhancement through physical or chemical mechanisms. While many preclinical studies have shown nanoparticle radiosensitization, most have focused on normoxic conditions, leaving the impact of hypoxia on nanoparticle-mediated dose enhancement unclear. Here, we report on physical and chemical dose enhancement of Au and TiO₂ nanoparticles, along with their efficacy in sensitizing normoxic and hypoxic fibrosarcoma cells. Photo- and radiocatalytic activities improved in hypoxia, while electron paramagnetic resonance spin traps confirmed hydroxyl radicals. Radiotherapy efficacy and DNA damage in HT1080 cells were evaluated under varying oxygen concentrations using preclinical and clinical X-ray sources. Our findings indicate a slight reduction in the physical dose enhancement of Au nanoparticles and an increase in the chemical dose enhancement of TiO₂ in hypoxia, suggesting a critical role of ROS in overcoming hypoxic radioresistance.

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