TY  - JOUR
AB  - This article represents the first foray into investigating the consequences of various material combinations on the short-wave infrared (SWIR, 1000-2000 nm) performance of Tm-based core-shell nanocrystals (NCs) above 1600 nm. In total, six different material combinations involving two different types of SWIR-emitting core NCs (α-NaTmF4 and LiTmF4) combined with three different protecting shell materials (α-NaYF4, CaF2, and LiYF4) have been synthesized. All corresponding homo- and heterostructured NCs have been meticulously characterized by powder X-ray diffraction and electron microscopy techniques. The latter revealed that out of the six investigated combinations, only one led to the formation of a true core-shell structure with well-segregated core and shell domains. The direct correlation between the downshifting performance and the spatial localization of Tm3+ ions within the final homo- and heterostructured NCs is established. Interestingly, to achieve the best SWIR performance, the formation of an abrupt interface is not a prerequisite, while the existence of a pure (even thin) protective shell is vital. Remarkably, although all homo- and heterostructured NCs have been synthesized under the exact same experimental conditions, Tm3+ SWIR emission is either fully quenched or highly efficient depending on the type of material combination. The most efficient combination (LiTmF4/LiYF4) achieved a high photoluminescence quantum yield of 39% for SWIR emission above 1600 nm (excitation power density in the range 0.5-3 W/cm2) despite significant intermixing. From now on, highly efficient SWIR-emitting probes with an emission above 1600 nm are within reach to unlock the full potential of in vivo SWIR imaging.
AU  - Arteaga Cardona, F.*
AU  - Madirov, E.*
AU  - Popescu, R.*
AU  - Wang, D.*
AU  - Busko, D.*
AU  - Ectors, D.*
AU  - Kübel, C.*
AU  - Eggeler, Y.M.*
AU  - Arus, B.A.
AU  - Chmyrov, A.
AU  - Bruns, O.T.
AU  - Richards, B.S.*
AU  - Hudry, D.*
C1  - 71709
C2  - 56382
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
TI  - Dramatic impact of materials combinations on the chemical organization of core-shell nanocrystals: Boosting the Tm3+ emission above 1600 nm.
JO  - ACS Nano
PB  - Amer Chemical Soc
PY  - 2024
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coating of polyethylene imine/hyaluronic acid were combined to construct a multifunctional nanoplatform, denoted as TCPH nanoparticles (NPs), for comprehensive cancer theranostics. TCPH NPs are featured by intrinsic functions including efficient reactive oxygen species (ROS) production, good photothermal conversion, programmed death-ligand 1 (PD-L1)-eliminating capability, and effective intracellular transport. The generated ROS and hyperthermia do not only achieve primary tumor elimination but also regulate the tumor immune microenvironment. Genomic disruption of PD-L1 conspicuously augments its therapeutic efficacy, especially in tumor metastasis and recurrence. Exceptional multimodal imaging navigation has also been developed. Excellent theranostics performance was substantiated in diverse tumor models, implying that this synergistic strategy of phototheranostics and immunotherapy provides a paradigm shift in emerging CRISPR-mediated nanomedicines.
AU  - Wang, Y.*
AU  - Chen, P.
AU  - Wen, H.*
AU  - Gui, X.*
AU  - Yan, D.*
AU  - Huang, D.*
AU  - Wang, D.*
C1  - 72442
C2  - 56643
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 33168−33180
TI  - Advanced nanoplatform mediated by CRISPR-Cas9 and aggregation-induced emission photosensitizers to boost cancer theranostics.
JO  - ACS Nano
VL  - 18
IS  - 48
PB  - Amer Chemical Soc
PY  - 2024
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Ongoing research has highlighted the significance of the cross-play of macrophages and mesenchymal stem cells (MSCs). Lysine-specific demethylase 6B (KDM6B) has been shown to control osteogenic differentiation of MSCs by depleting trimethylated histone 3 lysine 27 (H3K27me3). However, to date, the role of KDM6B in bone marrow-derived macrophages (BMDMs) remains controversial. Here, a chromatin immunoprecipitation assay (ChIP) proved that KDM6B derived from osteogenic-induced BMSCs could bind to the promoter region of BMDMs' brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) gene in a coculture system and activate BMAL1. Transcriptome sequencing and experiments in vitro showed that the overexpression of BMAL1 in BMDM could inhibit the TLR2/NF-κB signaling pathway, reduce pyroptosis, and decrease the M1/M2 ratio, thereby promoting osteogenic differentiation of BMSCs. Furthermore, bone and macrophage dual-targeted GSK-J4 (KDM6B inhibitor)-loaded nanodiscs were synthesized via binding SDSSD-apoA-1 peptide analogs (APA) peptide, which indirectly proved the critical role of KDM6B in osteogenesis in vivo. Overall, we demonstrated that KDM6B serves as a positive circulation trigger during osteogenic differentiation by decreasing the ratio of M1/M2 both in vitro and in vivo. Collectively, these results provide insight into basic research in the field of osteoporosis and bone repair.
AU  - Chen, L.*
AU  - Yu, C.*
AU  - Xu, W.*
AU  - Xiong, Y.*
AU  - Cheng, P.*
AU  - Lin, Z.*
AU  - Zhang, Z.*
AU  - Knoedler, L.*
AU  - Panayi, A.C.*
AU  - Knoedler, S.
AU  - Wang, J.*
AU  - Mi, B.*
AU  - Liu, G.*
C1  - 67336
C2  - 54176
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 3153-3167
TI  - Dual-targeted nanodiscs revealing the cross-talk between osteogenic differentiation of mesenchymal stem cells and macrophages.
JO  - ACS Nano
VL  - 17
IS  - 3
PB  - Amer Chemical Soc
PY  - 2023
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention. In the MHV-68 mouse model, progressive lung inflammation and emphysema-like injury were detected 1 week after repetitive CNP and DWCNT exposure. NPs reactivated the latent herpesvirus mainly in CD11b+ macrophages in the lungs. In vitro, in persistently MHV-68 infected bone marrow-derived macrophages, ERK1/2, JNK, and p38 MAPK were rapidly activated after CNP and DWCNT exposure, followed by viral gene expression and increased viral titer but without generating a pro-inflammatory signature. Pharmacological inhibition of p38 activation abrogated CNP- but not DWCNT-triggered virus reactivation in vitro, and inhibitor pretreatment of latently infected mice attenuated CNP-exposure-induced pulmonary MHV-68 reactivation. Our findings suggest a crucial contribution of particle-exposure-triggered herpesvirus reactivation for nanomaterial exposure or air pollution related lung emphysema development, and pharmacological p38 inhibition might serve as a protective target to alleviate air pollution related chronic lung disease exacerbations. Because of the required precondition of latent infection described here, the use of single hit models might have severe limitations when assessing the respiratory toxicity of nanoparticle exposure.
AU  - Han, L.
AU  - Haefner, V.
AU  - Yu, Y.*
AU  - Han, B.*
AU  - Ren, H.
AU  - Irmler, M.
AU  - Beckers, J.
AU  - Liu, Q.
AU  - Feuchtinger, A.
AU  - Yildirim, A.Ö.
AU  - Adler, H.
AU  - Stöger, T.
C1  - 68718
C2  - 54927
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 21056-21072
TI  - Nanoparticle-exposure-triggered virus reactivation induces lung emphysema in mice.
JO  - ACS Nano
VL  - 17
IS  - 21
PB  - Amer Chemical Soc
PY  - 2023
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines, aromatic amines, and organohalogens, are known to affect both tumor characteristics and patient outcomes in lung squamous cell carcinoma (LUSC); however, the roles of these compounds in lung adenocarcinoma (LUAD) remain unclear. We analyzed 11 carbon-bound exogenous compounds in LUAD and LUSC samples using in situ high mass-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging and performed a cluster analysis to compare the patterns of carbon-bound exogenous compounds between these two lung cancer subtypes. Correlation analyses were conducted to investigate associations among exogenous compounds, endogenous metabolites, and clinical data, including patient survival outcomes and smoking behaviors. Additionally, we examined differences in exogenous compound patterns between normal and tumor tissues. Our analyses revealed that PAHs, aromatic amines, and organohalogens were more abundant in LUAD than in LUSC, whereas the tobacco-specific nitrosamine nicotine-derived nitrosamine ketone was more abundant in LUSC. Patients with LUAD and LUSC could be separated according to carbon-bound exogenous compound patterns detected in the tumor compartment. The same compounds had differential impacts on patient outcomes, depending on the cancer subtype. Correlation and network analyses indicated substantial differences between LUAD and LUSC metabolomes, associated with substantial differences in the patterns of the carbon-bound exogenous compounds. These data suggest that the contributions of these carcinogenic compounds to cancer biology may differ according to the cancer subtypes.
AU  - Shen, J.
AU  - Sun, N.
AU  - Wang, J.
AU  - Zens, P.*
AU  - Kunzke, T.
AU  - Buck, A.
AU  - Prade, V.M.
AU  - Wang, Q.
AU  - Feuchtinger, A.
AU  - Hu, R.*
AU  - Berezowska, S.*
AU  - Walch, A.K.
C1  - 67935
C2  - 54413
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 16396-16411
TI  - Patterns of carbon-bound exogenous compounds impact disease pathophysiology in lung cancer subtypes in different ways.
JO  - ACS Nano
VL  - 17
IS  - 17
PB  - Amer Chemical Soc
PY  - 2023
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Yttrium oxide nanoparticles (nY2O3), one of the broadly used rare earth nanoparticles, can interact with plants and possibly cause plant health and environmental impacts, but the plant defense response particularly at the nanoparticle-cell interface is largely unknown. To elucidate this, Bright Yellow 2 (BY-2) tobacco (Nicotiana tabacum L.) suspension-cultured cells were exposed to 50 mg L-1 nY2O3 (30 nm) for 12 h. Although 42.2% of the nY2O3 remained outside of protoplasts, nY2O3 could still traverse the cell wall and was partially deposited inside the vacuole. In addition to growth inhibition, morphological and compositional changes in cell walls occurred. Together with a locally thickened (7-13-fold) cell wall, increased content (up to 58%) of pectin and reduction in (up to 29%) hemicellulose were observed. Transcriptome analysis revealed that genes involved in cell wall metabolism and remodeling were highly regulated in response to nY2O3 stress. Expression of genes for pectin synthesis and degradation was up- and down-regulated by 31-78% and 13-42%, respectively, and genes for xyloglucan and pectin modifications were up- and down-regulated by 82% and 81-92%, respectively. Interestingly, vesicle trafficking seemed to be activated, enabling the repair and defense against nY2O3 disturbance. Our findings indicate that, although nY2O3 generated toxicity on BY-2 cells, it is very likely that during the recovery process cell wall remodeling was initiated to gain resistance to nY2O3 stress, demonstrating the plant's cellular regulatory machinery regarding repair and adaptation to nanoparticles like nY2O3.
AU  - Chen, F.*
AU  - Wang, C.*
AU  - Yue, L.*
AU  - Zhu, L.*
AU  - Tang, J.*
AU  - Yu, X.*
AU  - Cao, X.*
AU  - Schröder, P.
AU  - Wang, Z.*
C1  - 62766
C2  - 51022
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 13166–13177
TI  - Cell walls are remodeled to alleviate nY2O3 cytotoxicity by elaborate regulation of de Novo synthesis and vesicular transport.
JO  - ACS Nano
VL  - 15
IS  - 8
PB  - Amer Chemical Soc
PY  - 2021
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Energy transfer allows energy to be moved from one quantum emitter to another. If this process follows the Forster mechanism, efficient transfer requires the emitters to be extremely close (<10 nm). To increase the transfer range, nanophotonic structures have been explored for photon- or plasmon-mediated energy transfer. Here, we fabricate high-quality silver plasmonic resonators to examine long-distance plasmon-mediated energy transfer. Specifically, we design elliptical resonators that allow energy transfer between the foci, which are separated by up to 10 mu m. The geometry of the ellipse guarantees that all plasmons emitted from one focus are collected and channeled through different paths to the other focus. Thus, energy can be transferred even if a micrometer-sized defect obstructs the direct path between the focal points. We characterize the spectral and spatial profiles of the resonator modes and show that these can be used to transfer energy between green- and red-emitting colloidal quantum dots printed with subwavelength accuracy using electrohydrodynamic nanodripping. Rate-equation modeling of the time-resolved fluorescence from the quantum dots further confirms the long-distance energy transfer.
AU  - Antolinez, F.V.*
AU  - Winkler, J.M.*
AU  - Rohner, P.*
AU  - Kress, S.J.P.*
AU  - Keitel, R.C.*
AU  - Kim, D.K.*
AU  - Marques-Gallego, P.*
AU  - Cui, J.
AU  - Rabouw, F.T.*
AU  - Poulikakos, D.*
AU  - Norris, D.J.*
C1  - 56928
C2  - 47435
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 9048-9056
TI  - Defect-tolerant plasmonic elliptical resonators for long-range energy transfer.
JO  - ACS Nano
VL  - 13
IS  - 8
PB  - Amer Chemical Soc
PY  - 2019
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Multicolored gene reporters for light microscopy are indispensable for biomedical research, but equivalent genetic tools for electron microscopy (EM) are still rare despite the increasing importance of nanometer resolution for reverse engineering of molecular machinery and reliable mapping of cellular circuits. We here introduce the fully genetic encapsulin/cargo system of Quasibacillus thermotolerans (Qt), which in combination with the recently characterized encapsulin system from Myxococcus xanthus (Mx) enables multiplexed gene reporter imaging via conventional transmission electron microscopy (TEM) in mammalian cells. Cryo-electron reconstructions revealed that the Qt encapsulin shell self-assembles to nanospheres with T = 4 icosahedral symmetry and a diameter of similar to 43 nm harboring two putative pore regions at the 5-fold and 3-fold axes. We also found that upon heterologous expression in mammalian cells, the native cargo is autotargeted to the inner surface of the shell and exhibits ferroxidase activity leading to efficient intraluminal iron biomineralization, which enhances cellular TEM contrast. We furthermore demonstrate that the two differently sized encapsulins of Qt and Mx do not intermix and can be robustly differentiated by conventional TEM via a deep learning classifier to enable automated multiplexed EM gene reporter imaging.
AU  - Sigmund, F.
AU  - Pettinger, S.
AU  - Kube, M.*
AU  - Schneider, F.*
AU  - Schifferer, M.*
AU  - Schneider, S.*
AU  - Efremova, M.V.
AU  - Pujol-Martí, J.*
AU  - Aichler, M.
AU  - Walch, A.K.
AU  - Misgeld, T.*
AU  - Dietz, H.*
AU  - Westmeyer, G.G.
C1  - 56326
C2  - 47005
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 8114-8123
TI  - Iron-sequestering nanocompartments as multiplexed Electron Microscopy gene reporters.
JO  - ACS Nano
VL  - 13
IS  - 7
PB  - Amer Chemical Soc
PY  - 2019
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Deciphering biodistribution, biokinetics, and biological effects of nanoparticles (NPs) in entire organs with cellular resolution remains largely elusive due to the lack of effective imaging tools. Here, light sheet fluorescence microscopy in combination with optical tissue clearing was validated for concomitant three-dimensional mapping of lung morphology and NP biodistribution with cellular resolution in nondissected ex viva murine lungs. Tissue autofluorescence allowed for label-free, quantitative morphometry of the entire bronchial tree, acinar structure, and blood vessels. Co-registration of fluorescent NPs with lung morphology revealed significant differences in pulmonary NP distribution depending on the means of application (intratracheal instillation and ventilator-assisted aerosol inhalation under anesthetized conditions). Inhalation exhibited a more homogeneous NP distribution in conducting airways and acini indicated by a central-to-peripheral (C/P) NP deposition ratio of unity (0.98 +/- 0.13) as compared to a 2-fold enhanced central deposition (C/P = 1.98 +/- 0.37) for instillation. After inhalation most NPs were observed in the proximal part of the acini as predicted by computational fluid dynamics simulations. At cellular resolution patchy NP deposition was visualized in bronchioles and acini, but more pronounced for instillation. Excellent linearity of the fluorescence intensity dose response curve allowed for accurate NP dosimetry and revealed ca. 5% of the inhaled aerosol was deposited in the lungs. This single-modality imaging technique allows for quantitative co-registration of tissue architecture and NP biodistribution, which could accelerate elucidation of NP biokinetics and bioactivity within intact tissues, facilitating both nanotoxicology studies and the development of nanomedicines.
AU  - Yang, L.
AU  - Feuchtinger, A.
AU  - Möller, W.
AU  - Ding, Y.
AU  - Kutschke, D.
AU  - Möller, G.
AU  - Schittny, J.C.*
AU  - Burgstaller, G.
AU  - Hofmann, W.*
AU  - Stöger, T.
AU  - Razansky, D.
AU  - Walch, A.K.
AU  - Schmid, O.
C1  - 55088
C2  - 46038
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 1029-1041
TI  - Three-dimensional quantitative co-mapping of pulmonary morphology and nanoparticle distribution with cellular resolution in non-dissected murine lungs.
JO  - ACS Nano
VL  - 13
IS  - 2
PB  - Amer Chemical Soc
PY  - 2019
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - The increasing use of gold nanoparticles leads to a possible increase of exposure by inhalation. Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7-90 day old rats and their biokinetics in 60 day old ones. Wistar-Kyoto rats inhaled intratracheally 20 nm Au-195-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d(-1)) In contrast, AuNP-translocation across the air-blood barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver > soft issue > spleen > kidneys > skeleton > blood > uterus > heart > brain. The age independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air blood barrier appeared to be similar to that of humans for similar sized AuNP.
AU  - Kreyling, W.G.
AU  - Möller, W.
AU  - Holzwarth, U.*
AU  - Hirn, S.
AU  - Wenk, A.
AU  - Schleh, C.
AU  - Schäffler, M.
AU  - Haberl, N.
AU  - Gibson, N.*
AU  - Schittny, J.C.*
C1  - 54359
C2  - 45463
CY  - 1155 16th St, Nw, Washington, Dc 20036 Usa
SP  - 7771-7790
TI  - Age-dependent rat lung deposition patterns of inhaled 20 manometer gold nanoparticles and their quantitative biokinetics in adult rats.
JO  - ACS Nano
VL  - 12
IS  - 8
PB  - Amer Chemical Soc
PY  - 2018
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - We present an ultrasensitive technique for quantitative protein–protein interaction analysis in a two-dimensional format based on phase-separated, micropatterned membranes. Interactions between proteins captured to lipid probes via an affinity tag trigger partitioning into the liquid-ordered phase, which is readily quantified by fluorescence imaging. Based on a calibration with well-defined low-affinity protein–protein interactions, equilibrium dissociation constants >1 mM were quantified. Direct capturing of proteins from mammalian cell lysates enabled us to detect homo- and heterodimerization of signal transducer and activator of transcription proteins. Using the epidermal growth factor receptor (EGFR) as a model system, quantification of low-affinity interactions between different receptor domains contributing to EGFR dimerization was achieved. By exploitation of specific features of the membrane-based assay, the regulation of EGFR dimerization by lipids was demonstrated.
AU  - Beutel, O.*
AU  - Roder, F.*
AU  - Birkholz, O.*
AU  - Rickert, C.*
AU  - Steinhoff, H.*
AU  - Grzybek, M.
AU  - Coskun, Ü.
AU  - Piehler, J.*
C1  - 47413
C2  - 40543
SP  - 9783-9791
TI  - Two-dimensional trap for ultrasensitive quantification of transient protein interactions.
JO  - ACS Nano
VL  - 9
IS  - 10
PY  - 2015
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Nanoparticles allow for controlled and targeted drug delivery to diseased tissues and therefore bypass systemic side effects. Spatiotemporal control of drug release can be achieved by nanocarriers that respond to elevated levels of disease-specific enzymes. For example, matrix metalloproteinase 9 (MMP9) is overexpressed in tumors, is known to enhance the metastatic potency of malignant cells, and has been associated with poor prognosis of lung cancer. Here, we report the synthesis of mesoporous silica nanoparticles (MSNs) tightly capped by avidin molecules via MMP9 sequence-specific linkers to allow for site-selective drug delivery in high-expressing MMP9 tumor areas. We provide proof-of-concept evidence for successful MMP9-triggered drug release from MSNs in human tumor cells and in mouse and human lung tumors using the novel technology of ex vivo 3D lung tissue cultures. This technique allows for translational testing of drug delivery strategies in diseased mouse and human tissue. Using this method we show MMP9-mediated release of cisplatin, which induced apoptotic cell death only in lung tumor regions of Kras mutant mice, without causing toxicity in tumor-free areas or in healthy mice. The MMP9-responsive nanoparticles also allowed for effective combinatorial drug delivery of cisplatin and proteasome inhibitor bortezomib, which had a synergistic effect on the (therapeutic) efficiency. Importantly, we demonstrate the feasibility of MMP9-controlled drug release in human lung tumors.
AU  - van Rijt, S.H.
AU  - Bölükbas, D.A.*
AU  - Argyo, C.*
AU  - Datz, S.*
AU  - Lindner, M.
AU  - Eickelberg, O.
AU  - Königshoff, M.
AU  - Bein, T.*
AU  - Meiners, S.
C1  - 44009
C2  - 36687
CY  - Washington
SP  - 2377-2389
TI  - Protease-mediated release of chemotherapeutics from mesoporous silica nanoparticles to ex vivo human and mouse lung tumors.
JO  - ACS Nano
VL  - 9
IS  - 3
PB  - Amer Chemical Soc
PY  - 2015
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of 198Au-radio-labeled monodisperse, well-characterized, negatively charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1, 3, and 24 h, the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows that as AuNP get smaller, they are more likely to cross the air-blood barrier (ABB) depending strongly on the inverse diameter d-1 of their gold core, i.e., their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most, while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d -1 relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP that had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood, and excretion via urine further declined with d-1 of AuNP core. Translocation of 5, 18, and 80 nm AuNP is virtually complete after 1 h, while 1.4 nm AuNP continue to translocate until 3 h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge.
AU  - Kreyling, W.G.
AU  - Hirn, S.
AU  - Möller, W.
AU  - Schleh, C.
AU  - Wenk, A.
AU  - Celik, G.
AU  - Lipka, J.
AU  - Schäffler, M.
AU  - Haberl, N.
AU  - Johnston, B.D.
AU  - Sperling, R.A.*
AU  - Schmid, G.*
AU  - Simon, U.*
AU  - Parak, W.J.*
AU  - Semmler-Behnke, M.
C1  - 30600
C2  - 33746
CY  - Washington
SP  - 222-233
TI  - Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size.
JO  - ACS Nano
VL  - 8
IS  - 1
PB  - Amer Chemical Soc
PY  - 2014
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, via the synthesis of a library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of the AuNPs is demonstrated using a hierarchical approach including three biological systems of increasing complexity: in vitro cultured human cells, in vivo invertebrate (freshwater polyp, Hydra), and in vivo vertebrate (mouse) models. Our synthetic methodology involved fine-tuning of multiple structural and functional moieties. Selection of the most active functionalities was assisted step-by-step through functional testing that adopted this hierarchical strategy. Merging these chemical and biological approaches led to a safe, nonpathogenic, self-tracking, and universally valid nanocarrier that could be exploited for therapeutic RNAi.
AU  - Conde, J.*
AU  - Ambrosone, A.*
AU  - Sanz, V.*
AU  - Hernandez, Y.*
AU  - Marchesano, V.*
AU  - Tian, F.
AU  - Child, H.*
AU  - Berry, C.C.*
AU  - Ibarra, M.R.*
AU  - Baptista, P.V.*
AU  - Tortiglione, C.*
AU  - de la Fuente, J.M.*
C1  - 10713
C2  - 30463
SP  - 8316-8324
TI  - Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing.
JO  - ACS Nano
VL  - 6
IS  - 9
PB  - Amer. Chemical Soc.
PY  - 2012
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - Engineered nanoparticles (ENPs) are produced and used in increasing quantities for industrial products, food, and drugs. The fate of ENPs after usage and impact on health is less known. Especially as air pollution, suspended nanoparticles have raised some attention, causing diseases of the lung and cardiovascular system. Human health risks may arise from inhalation of ENPs with associated inflammation, dispersion in the body, and exposure of vulnerable organs (e.g., heart, brain) and tissues with associated toxicity. However, underlying mechanisms are largely unknown. Furthermore future use of ENPs in therapeutic applications is being researched. Therefore knowledge about potential cardiovascular risks due to exposure to ENPs is highly demanded, but there are no established biological testing models yet. Therefore, we established the isolated beating heart (Langendorff heart) as a model system to study cardiovascular effects of ENPs. This model enables observation and analysis of electrophysiological parameters over a minimal time period of 4 h without influence by systemic effects and allows the determination of stimulated release of substances under influence of ENPs. We found a significant dose and material dependent increase in heart rate accompanied by arrhythmia evoked by ENPs made of flame soot (Printex 90), spark discharge generated soot, anatas (TiO(2)), and silicon dioxide (SiO(2)). However, flame derived SiO(2) (Aerosil) and monodisperse polystyrene lattices exhibited no effects. The increase in heart rate is assigned to catecholamine release from adrenergic nerve endings within the heart. We propose the isolated Langendorff heart and its electrophysiological characterization as a suitable test model for studying cardiovascular ENP toxicity.
AU  - Stampfl, A.
AU  - Maier, M.
AU  - Radykewicz, R.
AU  - Reitmeir, P.
AU  - Göttlicher, M.
AU  - Niessner, R.
C1  - 6528
C2  - 28911
SP  - 5345-5353
TI  - Langendorff heart: A model system to study cardiovascular effects of engineered nanoparticles.
JO  - ACS Nano
VL  - 5
IS  - 7
PB  - Amer Chemical Soc
PY  - 2011
SN  - 1936-0851
ER  - 

TY  - JOUR
AB  - With very few exceptions, previous nanotoxicity studies implicitly involved the assumption that the techniques developed for risk assessment of hazardous chemical substances can be applied in unchanged form to explore cell response in NP laden media. This misleading approach has the consequence that the actual dose of exposure is ill defined or, more often, completely unknown. Here the effect of gravitational settling on the dose of exposure was explored for commercially available engineered nanostructured matter (nanopowder). Micrometer sized aggregates abundantly present in all nanopowders were fractured as much as possible by probe-type sonication in water or cell culture media. The morphology of cracked aggregates was studied by scanning electron microscopy. Size distributions were determined by dynamic light scattering (DLS). Possible pitfalls encountered in using DLS were documented. Absorbance measurements and optical microscopy served to monitor the rate of gravitational settling on time sales ranging from minutes up to several days. The sonicated particles settled rapidly in all liquid media. At the well bottom, they exhibited intense lateral (two-dimensional) Brownian-like motion, which allowed them to travel large distances. Taken together, the probability for particle-cell contact may be enhanced by a factor of more than 1000 compared to the commonly advocated picture. The very high levels of exposure can give rise to overload effects which are often misinterpreted as evidence of cytotoxicity. To identify the true toxic potential of NPs, future studies must account for these phenomena. It is also argued that stable dispersions of NPs are not required in nanotoxicity studies.
AU  - Wittmaack, K.
C1  - 4667
C2  - 28538
SP  - 3766-3778
TI  - Excessive delivery of nanostructured matter to submersed cells caused by rapid gravitational settling.
JO  - ACS Nano
VL  - 5
IS  - 5
PB  - Amer Chemical Soc
PY  - 2011
SN  - 1936-0851
ER  -