RNA-driven phase transitions in biomolecular condensates.

RNAs and RNA-binding proteins can undergo spontaneous or active condensation into phase-separated liquid-like droplets. These condensates are cellular hubs for various physiological processes, and their dysregulation leads to diseases. Although RNAs are core components of many cellular condensates, the underlying molecular determinants for the formation, regulation, and function of ribonucleoprotein condensates have largely been studied from a protein-centric perspective. Here, we highlight recent developments in ribonucleoprotein condensate biology with a particular emphasis on RNA-driven phase transitions. We also present emerging future directions that might shed light on the role of RNA condensates in spatiotemporal regulation of cellular processes and inspire bioengineering of RNA-based therapeutics.

ß-synuclein regulates the phase transitions and amyloid conversion of α-synuclein.

Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. ß-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that ß-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated ß-synuclein mutations lose these capacities. Exogenous ß-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated ß-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/ß-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and ß-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Sterol-lipids enable large-scale, liquid-liquid phase separation in bilayer membranes of only two components.

Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, some of which are present in bacteria, we found a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests an additional role for sterol-lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories.

Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.

Liquid-liquid phase transition as a basis for novel materials for skin repair and regeneration.

Inorganic materials are of increasing interest not only for bone repair but also for other applications in regenerative medicine. In this study, the combined effects of energy-providing, regeneratively active inorganic polyphosphate (polyP) and also morphogenetically active pearl powder on wound healing were investigated. Aragonite, the mineralic constituent of pearl nacre and thermodynamically unstable form of crystalline calcium carbonate, was found to be converted into a soluble state in the presence of a Ca2+-containing wound exudate, particularly upon addition of sodium polyP (Na-polyP), driven by the transfer of Ca2+ ions from aragonite to polyP, leading to liquid-liquid phase separation to form an aqueous Ca-polyP coacervate. This process is further enhanced in the presence of Ca-polyP nanoparticles (Ca-polyP-NP). Kinetic studies revealed that the coacervation of polyP and nacre aragonite in wound exudate is a very rapid process that results in the formation of a stronger gel with a porous structure compared to polyP alone. Coacervate formation, enabled by phase transition of crystalline aragonite in the presence of Na-polyP/Ca-polyP-NP and wound exudate, could also be demonstrated in a hydroxyethyl cellulose-based hydrogel used for wound treatment. Furthermore, it is shown that Na-polyP/Ca-polyP-NP together with nacre aragonite strongly enhances the proliferation of mesenchymal stem cells and promotes microtube formation in the in vitro angiogenesis assay with HUVEC endothelial cells. The latter effect was confirmed by gene expression studies, applying real-time polymerase chain reaction, using the biomarker genes VEGF (vascular endothelial growth factor) and hypoxia-inducible factor-1 α (HIF-1α). Division of Escherichia coli is suppressed when suspended in a matrix containing Na-polyP/Ca-polyP-NP and aragonite. The potential medical relevance of these findings is supported by an animal study on genetically engineered diabetic mice (db/db), which demonstrated a marked increase in granulation tissue and microvessel formation in regenerating experimental wounds treated with Ca-polyP-NP compared to controls. Co-administration of aragonite significantly accelerated the wound healing-promoting effect of polyP in db/db mice. Based on these results, we propose that the ability of polyP to form a mixed coacervate with aragonite, in addition to its energy (ATP)-generating function, can decisively contribute to the regenerative activity of this polymer in wound repair.

Phase Behavior Modulation of a Unary DNA Origami System through Allosteric Stimuli.

A unary system is the most conceptually concise design for conducting self-assembly. However, in most DNA-guided self-assembly schemes, a unary system has rarely been adopted because of the inherent challenge of strictly decoupling the monomer synthesis process from the assembly process, which may directly lead to the inaccurate control over assembly. Herein, we provide a multi-stimulus-triggered assembly strategy based on the DNA origami structure, which allows the unary system to realize controllable crystallization and phase transition by exerting allosteric stimuli. We intentionally introduced a specific DNA stimulus to convert the self-aggregation of functionalized groups into the connection of nearby monomers, thus producing multidimensional high-quality crystals. Furthermore, this unary system can undergo a phase transition from simple cubic to face-centered cubic with the introduction of more cation stimuli. We believe that this dynamic stimulation strategy can offer a novel solution for fabricating materials with on-demand modulation.

Phase separation of triton X-100 and bovine serum albumin mixture: Impacts of nature and composition of polyols on associated physicochemical parameters.

Bovine serum albumin (BSA) is widely used in tissue engineering and pharmaceutical research. It is readily available as a byproduct of the cattle industry, and collected from blood. In this study, we conducted a physicochemical investigation of the phase separation in a mixture of Triton X-100 (TX-100) and BSA, influenced by various polyols, using the well-established cloud point (CP) determination method. The addition of polyols resulted in a significant reduction in CP values for the TX-100 + BSA mixture. The magnitudes of CP in the experimental system were highly varied with different polyols and followed the order of: [Formula: see text] Under identical conditions, the system exhibited maximum solubility in the xylose solution and minimum solubility in the maltose solution. The positive ΔGc0 values were acquired in all working medium imply the nonspontaneity of phase transition in the TX-100 + BSA system. At lower polyol contents, the negative values of standard enthalpy (∆Hc0) and standard entropy (∆Sc0) changes were observed, suggesting that electrostatic forces dominated as the driving force for clouding. At highest employed polyols concentration in some case, the positive values for ∆Hc0 and ∆Sc0 were achieved, which indicated that hydrophobic interactions likely dominate the phase partitioning of the amphiphile and protein mixture. Additionally, entropy-enthalpy compensation parameters were calculated and analyzed with a rational approach. Molecular docking analysis further demonstrated the presence of hydrogen bonds and hydrophobic interactions between TX-100 and BSA.

Induction of the Interdigitated Gel Phase of Hydrated Dipalmitoylphosphatidylcholine Bilayers by the Artificial Sweetener Sucralose.

Recent research indicates that high doses of sucralose content can weaken the immune response in mice. To better understand the interaction between cell membranes and sucralose, we studied model biomembranes composed of dipalmitoylphosphatidylcholine bilayers in a sucralose solution. Calorimetry measurements showed that the effect of sucralose on the phase behavior is biphasic. Pretransitions and main transitions are decreased at low sucralose concentrations, while the main transition is increased at high concentrations. Pretransitions cannot be detected above the concentration at which the direction of change in the main transition temperature reverses. X-ray diffraction measurements revealed that sucralose at concentrations higher than 0.2 M induces the interdigitated gel (LßI) phase below the main transition temperature. Fluorescence Prodan measurements suggested that the sucralose solution is slightly more hydrophobic than the sucrose solution. This could be one reason why sucralose induces the LßI phase.

Unlocking Industrial Potential: Phase-Transition Coimmobilization of Multienzyme Systems for High-Efficiency Uridine Diphosphate Galactose Production.

Transitioning from batch to continuous industrial production often improves the economic returns and production efficiency. Immobilization is a critical strategy that can facilitate this shift. This study refined the previously established method for synthesizing uridine diphosphate galactose (UDP-Gal) by employing thermophilic enzymes. Three thermophilic enzymes (galactokinase, uridine diphosphate glucose pyrophosphorylase, and inorganic pyrophosphatase) were coimmobilized on the pH-responsive carrier Eudragit S-100, promoting enzyme recovery and reuse while their industrial potential was assessed. The coimmobilization system efficiently catalyzed UDP-Gal production, yielding 13.69 mM in 1.5 h, attaining a UTP conversion rate of 91.2% and a space-time yield (STY) of 5.16 g/L/h. Moreover, the system exhibited exceptional reproducibility, retaining 58.9% of its initial activity after five cycles. This research highlighted promising prospects for coimmobilization in industrial synthesis and proposed a novel methodology for enhancing UDP-Gal production in the industry. In addition, the phase-transition property of Eudragit S-100 paves the way for further exploration with the one-pot synthesis of poorly soluble galactosides.

Effect of Surface Freezing of Sodium Hexadecyl Sulfate - Hexadecanol Mixed Adsorbed film on OW Emulsion Stability.

The adsorbed film of Sodium Hexadecyl Sulfate (SHS) at the dodecane - water interface showed a first-order phase transition to a surface frozen monolayer upon cooling by the lateral van der Waals attraction between their hydrophobic tails and those of hexadecanol (C16OH) incorporated from the dodecane phase. The surface freezing transition of the SHS - C16OH monolayer was then utilized to stabilize an oil-in-water (OW) emulsion. The obtained results were compared to those examined previously for the cetyltrimethylammonium chloride (CTAC) - C16OH surface frozen monolayer. The main conclusion of this study was that the interfacial density of SHS significantly increased at the surface freezing by the cooperative adsorption with C16OH which gave rise to a higher surface freezing temperature (35°C) compared to CTAC (25°C). The formation of the surface freezing monolayer in the ambient temperature range could have a significant importance when it is applied to practical applications.

Aggregation of the amyloid-ß peptide (Aß40) within condensates generated through liquid-liquid phase separation.

The deposition of the amyloid-ß (Aß) peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Recently, it has been reported that some proteins can aggregate and form amyloids through an intermediate pathway involving a liquid-like condensed phase. These observations prompted us to investigate the phase space of Aß. We thus explored the ability of Aß to undergo liquid-liquid phase separation, and the subsequent liquid-to-solid transition that takes place within the resulting condensates. Through the use of microfluidic approaches, we observed that the 40-residue form of Αß (Αß40) can undergo liquid-liquid phase separation, and that accessing a liquid-like intermediate state enables Αß40 to self-assemble and aggregate into amyloid fibrils through this pathway. These results prompt further studies to investigate the possible role of Αß liquid-liquid phase separation and its subsequent aggregation in the context of Alzheimer's disease and more generally on neurodegenerative processes.

Cross-Effects in Folding and Phase Transitions of hnRNP A1 and C9Orf72 RNA G4 In Vitro.

Abnormal intracellular phase transitions in mutant hnRNP A1 may underlie the development of several neurodegenerative diseases. The risk of these diseases increases upon C9Orf72 repeat expansion and the accumulation of the corresponding G-quadruplex (G4)-forming RNA, but the link between this RNA and the disruption of hnRNP A1 homeostasis has not been fully explored so far. Our aim was to clarify the mutual effects of hnRNP A1 and C9Orf72 G4 in vitro. Using various optical methods and atomic force microscopy, we investigated the influence of the G4 on the formation of cross-beta fibrils by the mutant prion-like domain (PLD) of hnRNP A1 and on the co-separation of the non-mutant protein with a typical SR-rich fragment of a splicing factor (SRSF), which normally drives the assembly of nuclear speckles. The G4 was shown to act in a holdase-like manner, i.e., to restrict the fibrillation of the hnRNP A1 PLD, presumably through interactions with the PLD-flanking RGG motif. These interactions resulted in partial unwinding of the G4, suggesting a helicase-like activity of hnRNP A1 RGG. At the same time, the G4 was shown to disrupt hnRNP A1 co-separation with SRSF, suggesting its possible contribution to pathology through interference with splicing regulation.

Silk Fabrics Modified with Photothermal Phase Change Microcapsules for Personal Thermal Management.

Introduction: With the development of technology, personal heat management has become a focus of attention. Phase change fabrics, as intelligent materials, are expected to be widely used in multiple fields, bringing comfortable, intelligent and convenient living experience. Methods: In this study, miniature phase change microcapsules (MPCM) with n-octadecane as core and poly(methyl methacrylate) as shell were successfully prepared. Using the in-situ reduction property of polydopamine, gold nanoparticles were deposited on the surface of the microcapsules, which retained the heat storage function and imparted photothermal and antibacterial properties. The MPCM with photothermal conversion function was modified on the surface of silk fabric using aqueous polyurethane after verified by comprehensive material characterisation techniques. Results: Under the near infrared light of 808 nm wavelength and 0.134 W/cm² irradiation intensity, the MPCM@PDA@Au modified silk fabrics showed excellent photothermal conversion performance, which could be increased from 25°C to 60°C in 50s. After the light source was cut off, the fabrics showed good heat release ability, with melting enthalpy and crystallisation enthalpy reaching 41.58 J/g and 43.3 J/g, respectively, which were not changed after repeated cycles. After the light source is cut off, the fabric has good heat release ability, and the enthalpy of melting and crystallisation reaches 41.58 J/g and 43.3 J/g, respectively, and the photothermal efficiency remains unchanged after many cycles of use, which proves that it has excellent durability and stability. The antimicrobial test shows that the fabric has significant antibacterial effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Discussion: MPCM@PDA@Au silk fabrics bring new possibilities for the future of personal thermal management and antimicrobial protection in the field of medical health, outdoor sports and other areas of broad application prospects, heralding the birth of a series of innovative applications and solutions.

Brillouin Biosensing of Viscoelasticity across Phase Transitions in Ovine Cornea.

Noninvasive in situ monitoring of viscoelastic characteristics of corneal tissue at elevated temperatures is pivotal for mechanical property-informed refractive surgery techniques, including thermokeratoplasty and photorefractive keratectomy, requiring precise thermal modifications of the corneal structure during these surgical procedures. This study harnesses Brillouin light scattering spectroscopy as a biosensing platform to noninvasively probe the viscoelastic properties of ovine corneas across a temperature range of 25-64 °C. By submerging the tissue samples in silicone oil, consistent hydration and immiscibility are maintained, allowing for their accurate sensing of temperature-dependent mechanical behaviors. We identify significant phase transitions in the corneal tissue, particularly beyond 40 °C, likely due to collagen unfolding, marking the beginning of thermal destabilization. A subsequent transition, observed beyond 60 °C, correlates with collagen denaturation. These phase transformations highlight the cornea's sensitivity to both physiologically reversible and irreversible viscoelastic changes induced by mild to high temperatures. Our findings underscore the potential of the Brillouin biosensing technique for real-time diagnostics of corneal biomechanics during refractive surgeries to attain optimized therapeutic outcomes.

Reorientation of interfacial water molecules during melting of brain sphingomyelin is associated with the phase transition of its C24:1 sphingomyelin lipids.

Melting of brain sphingomyelin (bSM) manifests as a broad feature in the DSC curve that encompasses the temperature range of 25 - 45 °C, with two distinguished maxima originating from the phase transitions of two the most abundant components: C24:1 (Tm,1) and C18:0 (Tm,2). While C24:1/C18:0 sphingomyelin transforms from the gel/ripple phase to the fluid/fluid phase, the dynamics of water molecules in the interfacial layer remain completely unknown. Therefore, we carried out a calorimetric (DSC), spectroscopic (temperature-dependent UV-Vis and fluorescence) and MD simulation study of bSM in the absence/presence of Laurdan® (bSM ± L) suspended in Britton-Robinson buffer with three different pH values, 4 (BRB4), 7 (BRB7) and 9 (BRB9), and of comparable ionic strength (I = 100 mM). According to DSC, T̅m, 1 (≈ 34.5 °C/≈ 32.1 °C) and T̅m, 2 (≈ 38.0 °C/≈ 37.2 °C) of bSM suspended in BRB4, BRB7, and BRB9 in the absence/presence of Laurdan® are found to be practically pH-independent. Turbidity-based data (UV-Vis) detected both qualitative and quantitative differences in the response of bSM suspended in BRB4/BRB7/BRB9 (T̅m: ∼ 35 °C/32.0 ± 0.2 °C/36.4 ± 0.4), suggesting an intricate interplay of weakening of van der Waals forces between their hydrocarbon chains and of increased hydration in the polar headgroups region during melting. The temperature-dependent response of Laurdan® reported a discontinuous, pH-dependent change in the reorientation of interfacial water molecules that coincides with the melting of C24:1 lipids (on average, T̅m (LTC/HTC): ≈ 31.8 °C/30.6 °C/30.5 °C). MD simulations elucidated the impact of Laurdan® on a change in the physicochemical properties of bSM lipids and characterized the hydrogen bond network at the interface at 20 °C and 50 °C.

Synthesis, the Reversible Isostructural Phase Transition, and the Dielectric Properties of a Functional Material Based on an Aminobenzimidazole-Iron Thiocyanate Complex.

By introducing disordered molecules into a crystal structure, the motion of the disordered molecules easily induces the formation of multidimensional frameworks in functional crystal materials, allowing for structural phase transitions and the realization of various dielectric properties within a certain temperature range. Here, we prepared a novel ionic complex [C7H8N3]3[Fe(NCS)6]·H2O (1) between 2-aminobenzimidazole and ferric isothiocyanate from ferric chloride hexahydrate, ammonium thiocyanate, and 2-aminobenzimidazole using the evaporation of the solvent method. The main components, the single-crystal structure, and the thermal and dielectric properties of the complex were characterized using infrared spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder XRD, thermogravimetric analysis, differential scanning calorimetry, variable-temperature and variable-frequency dielectric constant tests, etc. The analysis results indicated that compound 1 belongs to the P21/n space group. Within the crystal structure, the [Fe(NCS)6]3- anion formed a two-dimensional hydrogen-bonded network with the organic cation through S···S interactions and hydrogen bonding. The disorder-order motion of the anions and cations within the crystal and the deformation of the crystal frameworks lead to a significant reversible isostructural phase transition and multiaxial dielectric anomalies of compound 1 at approximately 240 K.

Viscosity Regulation of Chemically Simple Condensates.

This study investigates the viscosity and liquid-solid transition behavior of biomolecular condensates formed by polyarginine chains (Rx) of varying lengths and citric acid (CA) derivatives. By condensing Rx chains of various lengths with CA derivatives, we showed that the shorter Rx chains attenuate the high aggregation tendency of the longer chains when condensed with CA. A mixture of different Rx lengths exhibited uniform intracondensate distribution, while its mobility largely depended on the ratio of the longer Rx chain. Our findings demonstrate a simple method to modulate condensate properties by adjusting the composition of scaffold molecules, shedding light on the role of molecular composition in controlling condensate viscosity and transition dynamics. This research contributes to a deeper understanding of biomolecular condensation processes and offers insights into potential strategies for manipulating condensate properties for various applications, including in the fields of synthetic biology and disease therapeutics in the future.

Adsorption of ciprofloxacin from aqueous solutions using cellulose-based adsorbents prepared by sol-gel method.

Ciprofloxacin (CIP) is one of the most widely used antibiotics to treat bacterial infections. Consequently, there is concern that it may contaminate water resources due to its high usage level. It is therefore necessary to monitor, trace, and reduce exposure to these antibiotic residues. In the current study, the extraction of CIP from water was performed using a green adsorbent material based on cellulose/polyvinyl alcohol (PVA) decorated with mixed metal oxides (MMO). This cellulose/MMO/PVA adsorbent was synthesized using a simple sol-gel method. The prepared adsorbent materials were then characterized using a range of methods, including scanning electron microscopy, energy-dispersive X-ray spectroscopy, gas adsorption analysis, X-ray diffraction, and Fourier Transform infrared. The impact of pH, adsorbent dose, contact time, and CIP concentration on ciprofloxacin extraction were examined. The equilibrium and kinetic adsorption data were well described using the Freundlich model (R2 = 0.965). The optimum conditions for CIP adsorption were: pH = 4.5; adsorbent dosage = 0.55 g·L-1; contact time = 83 min; and initial CIP concentration = 2 mg·L-1. The adsorption capacity of the cellulose/MMO/PVA adsorbent for CIP removal was ∼19 mg·g-1 (CIP removal = 86.48 %). This study shows that cellulose/MMO/PVA adsorbents have potential for removing contaminants from aqueous environments.

Water phase transition and signal nulling in 3D dual-echo adiabatic inversion-recovery UTE (IR-UTE) imaging of myelin.

PURPOSE: The semisolid myelin sheath has very fast transverse relaxation and is invisible to conventional MRI sequences. UTE sequences can detect signal from myelin. The major challenge is the concurrent detection of various water components. METHODS: The inversion recovery (IR)-based UTE (IR-UTE) sequence employs an adiabatic inversion pulse to invert and suppress water magnetizations. TI plays a key role in water suppression, with negative water magnetizations (negative phase) before the null point and positive water magnetizations (positive phase) after the null point. A series of dual-echo IR-UTE images were acquired with different TIs to detect water phase transition. The effects of TR in phase transition and water suppression were also investigated using a relatively long TR of 500 ms and a short TR of 106 ms. The water phase transition in dual-echo IR-UTE imaging of myelin was investigated in five ex vivo and five in vivo human brains. RESULTS: An apparent phase transition was observed in the second echo at the water signal null point, where the myelin signal was selectively detected by the UTE data acquisition at the optimal TI. The water phase transition point varied significantly across the brain when the long TR of 500 ms was used, whereas the convergence of TIs was observed when the short TR of 106 ms was used. CONCLUSION: The results suggest that the IR-UTE sequence with a short TR allows uniform inversion and nulling of water magnetizations, thereby providing volumetric imaging of myelin.

Sol-gel synthesis of magnesium oxide nanoparticles and their evaluation as a therapeutic agent for the treatment of osteoarthritis.

Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA).Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model.Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250 µg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage.Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome.

[Box: see text].