Cross-linked antioxidant nanozymes for improved delivery to CNS

Formulations of antioxidant enzymes, superoxide dismutase 1 (SOD1, also known as Cu/Zn SOD) and catalase were prepared by electrostatic coupling of enzymes with cationic block copolymers, polyethyleneimine-poly(ethylene glycol) or poly(L-lysine)-poly(ethylene glycol), followed by covalent cross-linking to stabilize nanoparticles (NPs). Different cross-linking strategies (using glutaraldehyde, bis-(sulfosuccinimidyl)suberate sodium salt or 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride with N-hydroxysulfosuccinimide) and reaction conditions (pH and polycation/protein charge ratio) were investigated that allowed immobilizing active enzymes in cross-linked NPs, termed "nanozymes." Bienzyme NPs, containing both SOD1 and catalase were also formulated. Formation of complexes was confirmed using denaturing gel electrophoresis and western blotting; physicochemical characterization was conducted using dynamic light scattering and atomic force microscopy. In vivo studies of 125I-labeled SOD1-containing nanozymes in mice demonstrated their increased stability in both blood and brain and increased accumulation in brain tissues, in comparison with non-cross-linked complexes and native SOD1. Future studies will evaluate the potential of these formulations for delivery of antioxidant enzymes to the central nervous system to attenuate oxidative stress associated with neurological diseases. From the Clinical Editor: Formulations of antioxidant enzyme complexes were demonstrated along with their increased stability in both blood and brain and increased accumulation in CNS tissue. Future studies will evaluate the potential of these formulations for antioxidant enzyme deliver to the CNS to attenuate oxidative stress in neurodegenerative diseases

Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles

Background: We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinsons disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme) then parenterally injected protect the nigrostriatum in a murine model of Parkinsons disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in macrophages. Methods: We examined relationships between the composition and structure of block ionomer complexes with a range of block copolymers, their physicochemical characteristics, and loading, release and catalase enzymatic activity in bone marrow-derived macrophages. Results: Formation of block ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with -polylysine and poly(L-glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates. However, these formulations did not efficiently protect catalase inside macrophages. Conclusion: Nanozymes with polyethyleneimine- and poly(L-lysine) 10-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery

Ultralight vector dark matter search using data from the KAGRA O3GK run

International audienceAmong the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for $U(1)_{B-L}$ gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the $U(1)_{B-L}$ gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Ultralight vector dark matter search using data from the KAGRA O3GK run

International audienceAmong the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for $U(1)_{B-L}$ gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the $U(1)_{B-L}$ gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Ultralight vector dark matter search using data from the KAGRA O3GK run

International audienceAmong the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for $U(1)_{B-L}$ gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the $U(1)_{B-L}$ gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Ultralight vector dark matter search using data from the KAGRA O3GK run

International audienceAmong the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for $U(1)_{B-L}$ gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the $U(1)_{B-L}$ gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Ultralight vector dark matter search using data from the KAGRA O3GK run

International audienceAmong the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for $U(1)_{B-L}$ gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the $U(1)_{B-L}$ gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Observation of Gravitational Waves from the Coalescence of a 2.5−4.5 M⊙2.5-4.5~M_\odot Compact Object and a Neutron Star

International audienceWe report the observation of a coalescing compact binary with component masses $2.5-4.5~M_\odot$ and $1.2-2.0~M_\odot$ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO-Virgo-KAGRA detector network on 2023 May 29 by the LIGO Livingston Observatory. The primary component of the source has a mass less than $5~M_\odot$ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We estimate a merger rate density of $55^{+127}_{-47}~\text{Gpc}^{-3}\,\text{yr}^{-1}$ for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star-black hole merger, GW230529_181500-like sources constitute about 60% of the total merger rate inferred for neutron star-black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star-black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap