TY  - JOUR
AB  - Magnetic nanoparticles have proven invaluable for biomechanical investigations due to their ability to exert localized forces. However, cellular delivery of exogenous magnetic agents often results in endosomal entrapment, thereby limiting their utility for manipulating subcellular structures. This study characterizes and exploits fully genetically controlled biomineralization of iron-oxide cores inside encapsulin nanocompartments to enable magnetic-activated cell sorting (MACS) and magnetic cell manipulation. The fraction of MACS-retained cells showed substantial overexpression of encapsulins and exhibited both para- and ferrimagnetic responses with magnetic moments of 10-15 A m2 per cell, comparable to standard exogenous labels for MACS. Electron microscopy revealed that MACS-retained cells contained densely packed agglomerates of approximate to 30 nm iron oxide cores consisting of ultrafine quasicrystalline ordered nuclei within an amorphous matrix of iron, oxygen, and phosphorus. Scanning transmission X-ray microscopy, X-ray absorption spectroscopy, and Raman microspectroscopy confirmed that the iron-oxide species are consistent with ferric oxide (Fe2O3). In addition, the encapsulin-overexpressing MACS-retained cells can be manipulated by a magnetic needle and regrown in patterns determined by magnetic gradients. This study demonstrates that the formation of quasicrystalline iron oxide with mixed para/ferrimagnetic behavior in the cytosol of mammalian cells enables magnetic manipulation without the delivery of exogenous agents.
AU  - Efremova, M.V.
AU  - Wiedwald, U.*
AU  - Sigmund, F.
AU  - Bodea, S.V.
AU  - Ohldag, H.*
AU  - Feggeler, T.*
AU  - Meckenstock, R.U.*
AU  - Panzl, L.N.
AU  - Francke, J.*
AU  - Beer, I.*
AU  - Ivleva, N.P.*
AU  - Alieva, I.B.*
AU  - Garanina, A.S.*
AU  - Semkina, A.S.*
AU  - Curdt, F.*
AU  - Josten, N.*
AU  - Wintz, S.*
AU  - Farle, M.*
AU  - Lavrijsen, R.*
AU  - Abakumov, M.A.*
AU  - Winklhofer, M.*
AU  - Westmeyer, G.G.
C1  - 73120
C2  - 56919
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Genetically controlled iron oxide biomineralization in encapsulin nanocompartments for magnetic manipulation of a mammalian cell line.
JO  - Adv. Func. Mat.
VL  - 35
IS  - 13
PB  - Wiley-v C H Verlag Gmbh
PY  - 2025
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Nucleic acid therapeutics are poised to revolutionize the clinical treatment of diseases once considered undruggable. Although these therapeutic approaches hold significant promise, delivering the nucleic acid cargo remains challenging due to susceptibility to nuclease degradation. Among all carrier systems, polymers stand out for their high tunability and cost-effectiveness. However, their flexible structure greatly expands the chemical space, making experimental exploration both costly and time-consuming. Leveraging published data and machine learning methods provides a valuable strategy to address these issues. The present study demonstrates a way to merge data from multiple sources and uses this information to identify new polyesters that effectively deliver siRNA into lung cells. One newly discovered polymer is further examined in ex vivo experiments and tested in a mouse model. The results indicate that a polymer capable of silencing specific genes in vivo can be discovered through machine learning, circumventing an extensive trial-and-error process in the search for novel materials.
AU  - Sieber-Schaefer, F.*
AU  - Jiang, M.*
AU  - Kromer, A.P.E.*
AU  - Nguyen, A.*
AU  - Molbay, M.*
AU  - Pinto Carneiro, S.*
AU  - Juergens, D.*
AU  - Burgstaller, G.
AU  - Popper, B.*
AU  - Winkeljann, B.*
AU  - Merkel, O.M.*
C1  - 75007
C2  - 57692
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Machine learning-enabled polymer discovery for enhanced pulmonary siRNA delivery.
JO  - Adv. Func. Mat.
PB  - Wiley-v C H Verlag Gmbh
PY  - 2025
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Stable/efficient low-energy emitters for photon down-conversion in bio-hybrid light-emitting diodes (Bio-HLEDs) are still challenging, as the archetypal fluorescent protein (FP) mCherry has led to the best deep-red Bio-HLEDs with poor stabilities: 3 h (on-chip)/160 h (remote). Capitalizing on the excellent refolding under temperature/pH/chemical stress, high brightness, and high compatibility with polysaccharides of phycobiliproteins (smURFP), first-class low-energy emitting Bio-HLEDs are achieved. They outperform those with mCherry regardless of using reference polyethylene oxide (on-chip: 24 h vs. 3 h) and new biopolymer hydroxypropyl cellulose (HPC; on-chip: 44 h vs. 3 h) coatings. Fine optimization of smURFP-HPC-coatings leads to stable record devices (on-chip: 2600 h/108 days) compared to champion devices with perylene diimides (on-chip: <700 h) and artificial FPs (on-chip: 35 h). Finally, spectroscopy/computational/thermal assays confirm that device degradation is related to the photo-induced reduction of biliverdin to bilirubin. Overall, this study pinpoints a new family of biogenic emitters toward superior protein-based lighting.
AU  - Hasler, M.*
AU  - Patrian, M.*
AU  - Banda-Vázquez, J.A.*
AU  - Ferrara, S.*
AU  - Stiel, A.-C.
AU  - Fuenzalida-Werner, J.P.*
AU  - Costa, R.D.*
C1  - 68573
C2  - 53709
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Fully biogenic near-infrared phosphors: Phycobiliproteins and  cellulose at force toward highly efficient and stable bio-hybrid light-emitting diodes.
JO  - Adv. Func. Mat.
PB  - Wiley-v C H Verlag Gmbh
PY  - 2023
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV-visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.
AU  - Di Giosia, M.*
AU  - Solda, A.
AU  - Seeger, M.
AU  - Cantelli, A.*
AU  - Arnesano, F.*
AU  - Nardella, M.I.*
AU  - Mangini, V.*
AU  - Valle, F.*
AU  - Montalti, M.*
AU  - Zerbetto, F.*
AU  - Rapino, S.*
AU  - Calvaresi, M.*
AU  - Ntziachristos, V.
C1  - 61573
C2  - 50349
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - A bio-conjugated fullerene as a subcellular-targeted and multifaceted phototheranostic agent.
JO  - Adv. Func. Mat.
VL  - 31
IS  - 20
PB  - Wiley-v C H Verlag Gmbh
PY  - 2021
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(epsilon-)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (0.5 mu m) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air-liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell-stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F-actin cytoskeleton filaments and tight junctions while non-physiologic over-stretch induces cell apoptosis, activates inflammatory response (IL-8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.
AU  - Doryab, A.
AU  - Taskin, M.B.*
AU  - Stahlhut, P.*
AU  - Schröppel, A.
AU  - Wagner, D.E.*
AU  - Groll, J.*
AU  - Schmid, O.
C1  - 60849
C2  - 49612
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - A biomimetic, copolymeric membrane for cell-stretch experiments with pulmonary epithelial cells at the air-liquid interface.
JO  - Adv. Func. Mat.
PB  - Wiley-v C H Verlag Gmbh
PY  - 2020
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Mechanical stretch under both physiological (breathing) and pathophysiological (ventilator-induced) conditions is known to significantly impact all cellular compartments in the lung, thereby playing a pivotal role in lung growth, regeneration and disease development. In order to evaluate the impact of mechanical forces on the cellular level, in vitro models using lung cells on stretchable membranes have been developed. Only recently have some of these cell-stretching devices become suitable for air-liquid interface cell cultures, which is required to adequately model physiological conditions for the alveolar epithelium. To reach this goal, a multi-functional membrane for cell growth balancing biophysical and mechanical properties is critical to mimic (patho)physiological conditions. In this review, i) the relevance of cyclic mechanical forces in lung biology is elucidated, ii) the physiological range for the key parameters of tissue stretch in the lung is described, and iii) the currently available in vitro cell-stretching devices are discussed. After assessing various polymers, it is concluded that natural-synthetic copolymers are promising candidates for suitable stretchable membranes used in cell-stretching models. This work provides guidance on future developments in biomimetic in vitro models of the lung with the potential to function as a template for other organ models (e.g., skin, vessels).
AU  - Doryab, A.
AU  - Tas, S.*
AU  - Taskin, M.B.*
AU  - Yang, L.*
AU  - Hilgendorff, A.
AU  - Groll, J.*
AU  - Wagner, D.E.*
AU  - Schmid, O.
C1  - 56703
C2  - 47201
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Evolution of bioengineered lung models: Recent advances and challenges in tissue mimicry for studying the role of mechanical forces in cell biology.
JO  - Adv. Func. Mat.
VL  - 29
IS  - 39
PB  - Wiley-v C H Verlag Gmbh
PY  - 2019
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Early and comprehensive endoscopic detection of colonic dysplasia-the most clinically significant precursor lesion to colorectal adenocarcinoma-provides an opportunity for timely, minimally invasive intervention to prevent malignant transformation. Here, the development and evaluation of biodegradable near-infrared fluorescent silica nanoparticles (FSN) that have the potential to improve adenoma detection during fluorescence-assisted white-light colonoscopic surveillance in rodent and human-scale models of colorectal carcinogenesis is described. FSNs are biodegradable (t(1/2) of 2.7 weeks), well-tolerated, and enable detection and delineation of adenomas as small as 0.5 mm(2) with high tumor-to-background ratios. Furthermore, in the human scale, APC(1311/+) porcine model, the clinical feasibility and benefit of using FSN-guided detection of colorectal adenomas using video-rate fluorescence-assisted white-light endoscopy is demon-strated. Since nanoparticles of similar size (e.g., 100-150 nm) or composition (i.e., silica and silica/gold hybrid) have already been successfully translated to the clinic, and clinical fluorescent/white-light endoscopy systems are becoming more readily available, there is a viable path towards clinical translation of the proposed strategy for early colorectal cancer detection and prevention in high-risk patients.
AU  - Rogalla, S.*
AU  - Flisikowski, K.*
AU  - Gorpas, D.
AU  - Mayer, A.T.*
AU  - Flisikowska, T.*
AU  - Mandella, M.J.*
AU  - Ma, X.
AU  - Casey, K.M.*
AU  - Felt, S.A.*
AU  - Saur, D.*
AU  - Ntziachristos, V.
AU  - Schnieke, A.*
AU  - Contag, C.H.*
AU  - Gambhir, S.S.*
AU  - Harmsen, S.*
C1  - 57303
C2  - 47704
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - Biodegradable fluorescent nanoparticles for endoscopic detection of colorectal carcinogenesis.
JO  - Adv. Func. Mat.
VL  - 29
IS  - 51
PB  - Wiley-v C H Verlag Gmbh
PY  - 2019
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Imaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease-modifying drugs. To this end, a fluorescent resonance energy transfer-based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP-13) has been developed. This protease degrades type II collagen, a major matrix component of cartilage. The probe exhibits high catalytic efficiency (k(cat)/K-M = 6.5 x 10(5) m(-1) s(-1)) and high selectivity for MMP-13 over a set of nine MMPs. To achieve optimal in vivo pharmacokinetics and tissue penetration, the probe has been further conjugated to a linear l-polyglutamate chain of 30 kDa. The conjugate detects early biochemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the monitoring of in vivo efficacy of an orally bioavailable MMP-13 inhibitor, which effectively blocks cartilage degradation during the development of OA. This new polymer-probe can therefore be a useful tool in detecting early OA, disease progression, and in developing MMP-13-based disease-modifying drugs for OA.
AU  - Duro-Castano, A.*
AU  - Lim, N.H.*
AU  - Tranchant, I.*
AU  - Amoura, M.*
AU  - Beau, F.*
AU  - Wieland, H.*
AU  - Kingler, O.*
AU  - Hermann, M.*
AU  - Nazaré, M.*
AU  - Plettenburg, O.
AU  - Dive, V.*
AU  - Vicent, M.J.*
AU  - Nagase, H.*
C1  - 54309
C2  - 45462
CY  - Postfach 101161, 69451 Weinheim, Germany
TI  - In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy.
JO  - Adv. Func. Mat.
VL  - 28
IS  - 37
PB  - Wiley-v C H Verlag Gmbh
PY  - 2018
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - Nanomaterials are of enormous value for biomedical applications because of their customizable features. However, the material properties of nanomaterials can be altered substantially by interactions with tissue thus making it important to assess them in the specific biological context to understand and tailor their effects. Here, a genetically controlled system is optimized for cellular uptake of superparamagnetic ferritin and subsequent trafficking to lysosomes. High local concentrations of photoabsorbing magnetoferritin give robust contrast in optoacoustic imaging and allow for selective photoablation of cells overexpressing ferritin receptors. Genetically controlled uptake of the biomagnetic nanoparticles also strongly enhances third-harmonic generation due to the change of refractive index caused by the magnetite-protein interface of ferritins entrapped in lysosomes. Selective uptake of magnetoferritin furthermore enables sensitive detection of receptor-expressing cells by magnetic resonance imaging, as well as efficient magnetic cell sorting and manipulation. Surprisingly, a substantial increase in the blocking temperature of lysosomally entrapped magnetoferritin is observed, which allows for specific ablation of genetically defined cell populations by local magnetic hyperthermia. The subcellular confinement of superparamagnetic ferritins thus enhances their physical properties to empower genetically controlled interrogation of cellular processes with deep tissue penetration.
AU  - Massner, C.
AU  - Sigmund, F.
AU  - Pettinger, S.
AU  - Seeger, M.
AU  - Hartmann, C.*
AU  - Ivleva, N.P.*
AU  - Niessner, R.*
AU  - Fuchs, H.
AU  - Hrabě de Angelis, M.
AU  - Stelzl, A.
AU  - Koonakampully, N.L.
AU  - Rolbieski, H.
AU  - Wiedwald, U.*
AU  - Spasova, M.
AU  - Wurst, W.
AU  - Ntziachristos, V.
AU  - Winklhofer, M.*
AU  - Westmeyer, G.G.
C1  - 53257
C2  - 44424
TI  - Genetically controlled lysosomal entrapment of superparamagnetic ferritin for multimodal and multiscale imaging and actuation with low tissue attenuation.
JO  - Adv. Func. Mat.
VL  - 28
IS  - 19
PY  - 2018
SN  - 1616-301X
ER  - 

TY  - JOUR
AB  - To study the influence of colloidal stability on protein corona formation, gold nanoparticles are synthesized with five distinct surface modifications: coating with citric acid, bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt, thiol-terminated methoxy-polyethylene glycol, dodecylamine-grafted poly(isobutylene-alt-maleic anhydride), and dodecylamine-grafted poly(isobutylene-alt-maleic anhydride) conjugated with polyethylene glycol. The nanoparticles are incubated with serum or bronchoalveolar lavage fluid from C57BL/6 mice (15 min or 24 h) to assess the effect of differential nanoparticle surface presentation on protein corona formation in the air–blood barrier exposure pathway. Proteomic quantification and nanoparticle size measurements are used to assess protein corona formation. We show that surface modification has a clear effect on the size and the composition of the protein corona that is related to the colloidal stability of the studied nanoparticles. Additionally, differences in the composition and size of the protein corona are shown between biological media and duration of exposure, indicating evolution of the corona through this exposure pathway. Consequently, a major determinant of protein corona formation is the colloidal stability of nanoparticles in biological media and chemical or environmental modification of the nanoparticles alters the surface presentation of the functional epitope in vivo. Therefore, the colloidal stability of nanoparticles has a decisive influence on nano–bio interactions.
AU  - Johnston, B.D.
AU  - Kreyling, W.G.
AU  - Pfeiffer, C.*
AU  - Schäffler, M.
AU  - Sarioglu, H.
AU  - Ristig, S.*
AU  - Hirn, S.
AU  - Haberl, N.
AU  - Thalhammer, S.
AU  - Hauck, S.M.
AU  - Semmler-Behnke, M.
AU  - Epple, M.*
AU  - Hühn, J.*
AU  - del Pino, P.*
AU  - Parak, W.J.*
C1  - 52036
C2  - 43659
CY  - Weinheim
TI  - Colloidal stability and surface chemistry are key factors for the composition of the protein corona of inorganic gold nanoparticles.
JO  - Adv. Func. Mat.
VL  - 27
IS  - 42
PB  - Wiley-v C H Verlag Gmbh
PY  - 2017
SN  - 1616-301X
ER  -