Browsing by Author "Rix, Anne"
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- ItemBio-degradable highly fluorescent conjugated polymer nanoparticles for bio-medical imaging applications([London] : Nature Publishing Group UK, 2017) Repenko, Tatjana; Rix, Anne; Ludwanowski, Simon; Go, Dennis; Kiessling, Fabian; Lederle, Wiltrud; Kuehne, Alexander J. C.Conjugated polymer nanoparticles exhibit strong fluorescence and have been applied for biological fluorescence imaging in cell culture and in small animals. However, conjugated polymer particles are hydrophobic and often chemically inert materials with diameters ranging from below 50 nm to several microns. As such, conjugated polymer nanoparticles cannot be excreted through the renal system. This drawback has prevented their application for clinical bio-medical imaging. Here, we present fully conjugated polymer nanoparticles based on imidazole units. These nanoparticles can be bio-degraded by activated macrophages. Reactive oxygen species induce scission of the conjugated polymer backbone at the imidazole unit, leading to complete decomposition of the particles into soluble low molecular weight fragments. Furthermore, the nanoparticles can be surface functionalized for directed targeting. The approach opens a wide range of opportunities for conjugated polymer particles in the fields of medical imaging, drug-delivery, and theranostics.
- ItemMultimodal and multiscale optical imaging of nanomedicine delivery across the blood-brain barrier upon sonopermeation(Wyoming, NSW : Ivyspring, 2020) May, Jan-Niklas; Golombek, Susanne K.; Baues, Maike; Dasgupta, Anshuman; Drude, Natascha; Rix, Anne; Rommel, Dirk; Stillfried, Saskia von; Appold, Lia; Pola, Robert; Pechar, Michal; van Bloois, Louis; Storm, Gert; Kuehne, Alexander J.C.; Gremse, Felix; Theek, Benjamin; Kiessling, Fabian; Lammers, TwanRationale: The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Sonopermeation, which relies on the combination of ultrasound and microbubbles, has emerged as a powerful tool to permeate the BBB, enabling the extravasation of drugs and drug delivery systems (DDS) to and into the central nervous system (CNS). When aiming to improve the treatment of high medical need brain disorders, it is important to systematically study nanomedicine translocation across the sonopermeated BBB. To this end, we here employed multimodal and multiscale optical imaging to investigate the impact of DDS size on brain accumulation, extravasation and penetration upon sonopermeation. Methods: Two prototypic DDS, i.e. 10 nm-sized pHPMA polymers and 100 nm-sized PEGylated liposomes, were labeled with fluorophores and intravenously injected in healthy CD-1 nude mice. Upon sonopermeation, computed tomography-fluorescence molecular tomography, fluorescence reflectance imaging, fluorescence microscopy, confocal microscopy and stimulated emission depletion nanoscopy were used to study the effect of DDS size on their translocation across the BBB. Results: Sonopermeation treatment enabled safe and efficient opening of the BBB, which was confirmed by staining extravasated endogenous IgG. No micro-hemorrhages, edema and necrosis were detected in H&E stainings. Multimodal and multiscale optical imaging showed that sonopermeation promoted the accumulation of nanocarriers in mouse brains, and that 10 nm-sized polymeric DDS accumulated more strongly and penetrated deeper into the brain than 100 nm-sized liposomes. Conclusions: BBB opening via sonopermeation enables safe and efficient delivery of nanomedicine formulations to and into the brain. When looking at accumulation and penetration (and when neglecting issues such as drug loading capacity and therapeutic efficacy) smaller-sized DDS are found to be more suitable for drug delivery across the BBB than larger-sized DDS. These findings are valuable for better understanding and further developing nanomedicine-based strategies for the treatment of CNS disorders. © The author(s).
- ItemOptimizing the Geometry of Photoacoustically Active Gold Nanoparticles for Biomedical Imaging(Washington, DC : ACS, 2020) García-Álvarez, Rafaela; Chen, Lisa; Nedilko, Alexander; Sánchez-Iglesias, Ana; Rix, Anne; Lederle, Wiltrud; Pathak, Vertika; Lammers, Twan; von Plessen, Gero; Kostarelos, Kostas; Liz-Marzán, Luis M.; Kuehne, Alexander J.C.; Chigrin, Dmitry N.Photoacoustics is an upcoming modality for biomedical imaging, which promises minimal invasiveness at high penetration depths of several centimeters. For superior photoacoustic contrast, imaging probes with high photothermal conversion efficiency are required. Gold nanoparticles are among the best performing photoacoustic imaging probes. However, the geometry and size of the nanoparticles determine their photothermal efficiency. We present a systematic theoretical analysis to determine the optimum nanoparticle geometry with respect to photoacoustic efficiency in the near-infrared spectral range, for superior photoacoustic contrast. Theoretical predictions are illustrated by experimental results for two of the most promising nanoparticle geometries, namely, high aspect ratio gold nanorods and gold nanostars. Copyright © 2020 American Chemical Society.