Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions.

Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI) exemplify the complexities and diversities that complicate their early detection and the development of effective treatments. Amid these challenges, the emergence of nanotechnology and extracellular vesicles (EVs) signals a new dawn for treating and diagnosing CNS ailments. EVs are cellularly derived lipid bilayer nanosized particles that are pivotal in intercellular communication within the CNS and have the potential to revolutionize targeted therapeutic delivery and the identification of novel biomarkers. Integrating EVs with nanotechnology amplifies their diagnostic and therapeutic capabilities, opening new avenues for managing CNS diseases. This review focuses on examining the fascinating interplay between EVs and nanotechnology in CNS theranostics. Through highlighting the remarkable advancements and unique methodologies, we aim to offer valuable perspectives on how these approaches can bring about a revolutionary change in disease management. The objective is to harness the distinctive attributes of EVs and nanotechnology to forge personalized, efficient interventions for CNS disorders, thereby providing a beacon of hope for affected individuals. In short, the confluence of EVs and nanotechnology heralds a promising frontier for targeted and impactful treatments against CNS diseases, which continue to pose significant public health challenges. By focusing on personalized and powerful diagnostic and therapeutic methods, we might improve the quality of patients.

Developing MiR-133a Zipper Nanoparticles for Targeted Enhancement of Thermogenic Adipocyte Generation.

Existing delivery methods for RNAi therapeutics encounter challenges, including stability, specificity, and off-target effects, which restrict their clinical effectiveness. In this study, a novel miR-133a zipper nanoparticle (NP) system that integrates miRNA zipper technology with rolling circle transcription (RCT) to achieve targeted delivery and specific regulation of miR-133a in adipocytes, is presented. This innovative approach can greatly enhance the delivery and release of miR-133a zippers, increasing the expression of thermogenic genes and mitochondrial biogenesis. he miR-133a zipper NP is utilized for the delivery of miRNA zipper-blocking miR-133a, an endogenous inhibitor of Prdm16 expression, to enhance the thermogenic activity of adipocytes by modulating their transcriptional program. Inhibition of miR-133a through the miR-133a zipper NP leads to more significant upregulation of thermogenic gene expression (Prdm16 and Ucp1) than with the free miR-133a zipper strand. Furthermore, miR-133a zipper NPs increase the number of mitochondria and induce heat production, reducing the size of 3D adipose spheroids. In short, this study emphasizes the role of RNA NPs in improving RNAi stability and specificity and paves the way for broader applications in gene therapy. Moreover, this research represents a significant advancement in RNAi-based treatments, pointing toward a promising direction for future therapeutic strategies.

Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome.

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology. To demonstrate the feasibility of the developed technology, MAGE is applied to correct the mutated MeCP2 gene in induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) from a Rett syndrome patient. By combining magnetofection and magnetic-activated cell sorting, MAGE achieves higher multi-plasmid delivery (99.3%) and repairing efficiencies (42.95%) with significantly shorter incubation times than conventional transfection agents without size limitations on plasmids. The repaired iPSC-NPCs showed similar characteristics as wild-type neurons when they differentiated into neurons, further validating MAGE and its potential for future clinical applications. In short, the developed nanobio-combined CRISPR-Cas9 technology offers the potential for various clinical applications, particularly in stem cell therapies targeting different genetic diseases.

Ischemic and Inflammatory Ocular Adverse Events Following Different Types of Vaccination for COVID-19 and Their Incidence Analysis.

PURPOSE: To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination. METHODS: Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency. RESULTS: Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine. CONCLUSIONS: OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.

Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling.

The removal of dying cells, or efferocytosis, is an indispensable part of resolving inflammation. However, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant apoptotic cells expressing CD47 is developed. In both normal and inflammatory circumstances, CAR macrophages exhibit activity equivalent to antibody blockage. The surface of CAR macrophages is modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting the liver X receptor pathway to improve their cell effector activities. The combination of CAR and nanoparticle engineering activated lipid efflux pumps enhances cell debris clearance and reduces inflammation. It is further suggested that the undifferentiated CAR-Ms can transmigrate within a mico-fabricated vessel system. It is also shown that our CAR macrophage can act as a chimeric switch receptor (CSR) to withstand the immunosuppressive inflammatory environment. The developed platform has the potential to contribute to the advancement of next-generation cardiovascular disease therapies and further studies include in vivo experiments.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Effects of Topical Anti-Glaucoma Medications on Outcomes of Endoscopic Dacryocystorhinostomy: Comparison with Age- and Sex-Matched Controls.

BACKGROUND: This study analyzed the effects of topical anti-glaucoma medications on the surgical outcomes of endoscopic dacryocystorhinostomy (EDCR) in nasolacrimal duct obstruction (NLDO). METHODS: This retrospective study included patients who underwent EDCR for NLDO between September 2012 and April 2021. Thirty patients with topical anti-glaucoma medications and 90 age- and sex-matched controls were included. RESULTS: The success rate of EDCR was higher in the control group than in the anti-glaucoma group (97.8% vs. 86.7%, p = 0.034). Univariate and multivariate logistic regression analyses identified prostaglandin analogs as the most influential risk factor for EDCR success among anti-glaucoma medication ingredients (p = 0.005). The success rate of the group containing all four anti-glaucoma medication ingredients was statistically significant (p = 0.010). The success rate was significantly different in the group of patients who used anti-glaucoma medication for >24 months (p = 0.019). When multiplying the number of drug ingredients by the duration in months, the group > 69 showed a significantly decreased success rate (p = 0.022). Multivariate logistic regression analysis identified the number of anti-glaucoma medications as the most significant risk factor for EDCR success (odds ratio, 0.437; 95% confidence interval, 0.247 to 0.772; p = 0.004). CONCLUSIONS: The authors suggest that the anti-glaucoma medications might cause NLDO and increase the failure rate after EDCR. Therefore, when performing EDCR in patients using topical anti-glaucoma medications, surgeons should consider the possibility of increased recurrence after EDCR in clinical outcomes.

Van Der Waals Semiconductor Based Omnidirectional Bifacial Transparent Photovoltaic for Visual-Speech Photocommunication.

Omnidirectional photosensing is crucial in optoelectronic devices, enabling a wide field of view (wFoV) and leveraging potential applications for the Internet of Things in sensors, light fidelity, and photocommunication. The wFoV helps overcome the limitations of line-of-sight communication, and transparent photodetection becomes highly desirable as it enables the capture of optical information from various angles. Therefore, developing a photoelectric device with a 360° wFoV, ultra sensitivity to photons, power generation, and transparency is of utmost importance. This study utilizes a heterojunction of van der Waals SnS with Ga2 O3 to fabricate a transparent photovoltaic (TPV) device showing a 360° wFoV with bifacial onsite power production. SnS/Ga2 O3 heterojunction preparation consists of magnetron sputtering and is free from nanopatterning/nanostructuring to achieve the desired wFoV window device. The device exhibits a high average visible transmittance of 56%, generates identical power from bifacial illumination, and broadband fast photoresponse. Careful analysis of the device shows an ultra-sensitive photoinduced defect-modulated heterojunction and photocapacitance, revealed by the impedance spectroscopy, suggesting photon-flux driven charge diffusion. Leveraging the wFoV operation, the TPV embedded visual and speech photocommunication prototype demonstrated, aiming to help visually and auditory impaired individuals, promising an environmental-friendly sustainable future.

Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold.

Degeneration of fibrocartilaginous tissues is often associated with complex pro-inflammatory factors. These include reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all-in-one nanoscaffold-based 3D porous hybrid protein (3D-PHP) self-therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D-PHP nanoscaffold is synthesized by introducing a novel nanomaterial-templated protein assembly (NTPA) strategy. 3D-PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli-responsive drug release, disc-mimetic stiffness, and excellent biodegradability. Enzyme-like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf-NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D-PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long-term pain reduction. Therefore, self-therapeutic and epigenetic modulator-encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.

Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects. Nanoparticles (NPs) have extreme potential for enhancing therapeutic efficacy but require continued research to elucidate beneficial interventions for women cancer survivors. In short, nanotechnology-based approaches have emerged as promising strategies for preventing and treating chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy. NP-based drug delivery systems and therapeutics have shown potential for reducing the side effects of chemotherapeutics while improving drug efficacy. In this article, the latest nanotechnology approaches and their potential for the prevention and treatment of chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy in breast and ovarian cancer survivors are discussed.

A novel co-culture assay to evaluate the effects of sympathetic innervation on vascular smooth muscle differentiation.

Dedifferentiation of vascular smooth muscle cells (VSMCs) from a functional phenotype to an inverse synthetic phenotype is a symptom of cardiovascular disorders, such as atherosclerosis and hypertension. The sympathetic nervous system (SNS) is an essential regulator of the differentiation of vascular smooth muscle cells (VSMCs). In addition, numerous studies suggest that SNS also stimulates VSMCs to retain their contractile phenotype. However, the molecular mechanisms for this stimulation have not been thoroughly studied. In this study, we used a novel in vitro co-culture method to evaluate the effective cellular interactions and stimulatory effects of sympathetic neurons on the differentiation of VSMCs. We co-cultured rat neural-like pheochromocytoma cells (PC12) and rat aortic VSMCs with this method. Expression of VSMCs contractile genes, including smooth muscle actin (acta2), myosin heavy chain (myh11), elastin (eln), and smoothelin (smtn), were determined by quantitative real-time-PCR analysis as an indicator of VSMCs differentiation. Fold changes for specific contractile genes in VSMCs grown in vitro for seven days in the presence (innervated) and absence (non-innervated) of sympathetic neurons were 3.5 for acta2, 6.5 for myh11, 4.19 for eln, and 4 for smtn (normalized to Tata Binding Protein (TBP)). As a result, these data suggest that sympathetic innervation promotes VSMCs' contractile gene expression and also maintains VSMCs' functional phenotype.

Development of a Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration.

Effective therapeutic approaches to overcome the heterogeneous pro-inflammatory and inhibitory extracellular matrix (ECM) microenvironment are urgently needed to achieve robust structural and functional repair of severely wounded fibrocartilaginous tissues. Herein we developed a dynamic and multifunctional nanohybrid peptide hydrogel (NHPH) through hierarchical self-assembly of peptide amphiphile modified with biodegradable two-dimensional nanomaterials with enzyme-like functions. NHPH is not only injectable, biocompatible, and biodegradable but also therapeutic by catalyzing the scavenging of pro-inflammatory reactive oxygen species and promoting ECM remodeling. In addition, our NHPH method facilitated the structural and functional recovery of the intervertebral disc (IVD) after severe injuries by delivering pro-regenerative cytokines in a sustained manner, effectively suppressing immune responses and eventually restoring the regenerative microenvironment of the ECM. In parallel, the NHPH-enhanced nucleus pulposus cell differentiation and pain reduction in a rat nucleotomy model further validated the therapeutic potential of NHPH. Collectively, our advanced nanoscaffold technology will provide an alternative approach for the effective treatment of IVD degeneration as well as other fibrocartilaginous tissue injuries.

The effect of Nano-liposomal sodium nitrite on smooth muscle cell growth in a tissue-engineered small-diameter vascular graft.

BACKGROUND: Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts. METHOD: Using a custom-designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small-diameter vascular grafts. A chemical signal of sodium nitrite was applied to control smooth muscle cells' behavior under static and dynamic cell culture conditions. The thin film hydration approach was used to create nano-liposomes, which were then used as sodium nitrite carriers to control the drug release rate and enhance the amount of drug loaded into the liposomes. RESULTS: The ratio of 80:20:2 for DPPC: Cholesterol: PEG was determined as the optimum formulation of the liposome structure with high drug encapsulation efficiency (98%) and optimum drug release rate (the drug release rate was 40%, 65%, and 83% after 24, 48, and 72 h, respectively). MTT assay results showed an improvement in endothelial cell proliferation in the presence of nano-liposomal sodium nitrite (LNS) at the concentration of 0.5 µg/mL. Using a suitable concentration of liposomal sodium nitrite (0.5 µg/mL) put onto the constructed scaffold resulted in the controllable development of smooth muscle cells in the experiment. The culture of smooth muscle cells in a pulsatile perfusion bioreactor indicated that in the presence of synthesized liposomal sodium nitrite, the overgrowth of smooth muscle cells was inhibited in dynamic cell culture conditions. The mechanical properties of ECM graft were measured, and a multi-scale model with an accuracy of 83% was proposed to predict mechanical properties successfully. CONCLUSION: The liposomal drug-loaded small-diameter vascular graft can prevent the overgrowth of SMCs and the formation of intimal hyperplasia in the graft. Aside from that, the effect of LNS on endothelial has the potential to stimulate endothelial cell proliferation and re-endothelialization.

Nanoparticle-Based Artificial Mitochondrial DNA Transcription Regulator: MitoScript.

The growing knowledge of the links between aberrant mitochondrial gene transcription and human diseases necessitates both an effective and dynamic approach to control mitochondrial DNA (mtDNA) transcription. To address this challenge, we developed a nanoparticle-based synthetic mitochondrial transcription regulator (MitoScript). MitoScript provides great colloidal stability, excellent biocompatibility, efficient cell uptake, and selective mitochondria targeting and can be monitored in live cells using near-infrared fluorescence. Notably, MitoScript controlled mtDNA transcription in a human cell line in an effective and selective manner. MitoScript targeting the light strand promoter region of mtDNA resulted in the downregulation of ND6 gene silencing, which eventually affected cell redox status, with considerably increased reactive oxygen species (ROS) generation. In summary, we developed MitoScript for the efficient, nonviral modification of mitochondrial DNA transcription. Our platform technology can potentially contribute to understanding the fundamental mechanisms of mitochondrial disorders and developing effective treatments for mitochondrial diseases.

Investigation of electrical stimulation on phenotypic vascular smooth muscle cells differentiation in tissue-engineered small-diameter vascular graft.

In the development of vascular tissue engineering, particularly in the case of small diameter vessels, one of the key obstacles is the blockage of these veins once they enter the in vivo environment. One of the contributing factors to this problem is the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) from the media layer of the artery to the interior of the channel. Two distinct phenotypes have been identified for smooth muscle cells, namely synthetic and contractile. Since the synthetic phenotype plays an essential role in the unusual growth and migration, the aim of this study was to convert the synthetic phenotype into the contractile one, which is a solution to prevent the abnormal growth of VSMCs. To achieve this goal, these cells were subjected to electrical signals, using a 1000 µA sinusoidal stimulation at 10 Hz for four days, with 20 min duration per 24 h. The morphological transformations and changes in the expression of vimentin, nestin, and ß-actin proteins were then studied using ICC and flow cytometry assays. Also, the expression of VSMC specific markers such as smooth muscle myosin heavy chain (SMMHC) and smooth muscle alpha-actin (α-SMA) were evaluated using RT-PCR test. In the final phase of this study, the sheep decellularized vessel was employed as a scaffold for seeding these cells. Based on the results, electrical stimulation resulted in some morphological alterations in VSMCs. Furthermore, the observed reductions in the expression levels of vimentin, nestin and ß-actin proteins and increase in the expression of SMMHC and α-SMA markers showed that it is possible to convert the synthetic phenotype to the contractile one using the studied regime of electrical stimulation. Finally, it can be concluded that electrical stimulation can significantly affect the phenotype of VSMCs, as demonstrated in this study.

Advanced theragnostics for the central nervous system (CNS) and neurological disorders using functional inorganic nanomaterials.

Various types of inorganic nanomaterials are capable of diagnostic biomarker detection and the therapeutic delivery of a disease or inflammatory modulating agent. Those multi-functional nanomaterials have been utilized to treat neurodegenerative diseases and central nervous system (CNS) injuries in an effective and personalized manner. Even though many nanomaterials can deliver a payload and detect a biomarker of interest, only a few studies have yet to fully utilize this combined strategy to its full potential. Combining a nanomaterial's ability to facilitate targeted delivery, promote cellular proliferation and differentiation, and carry a large amount of material with various sensing approaches makes it possible to diagnose a patient selectively and sensitively while offering preventative measures or early disease-modifying strategies. By tuning the properties of an inorganic nanomaterial, the dimensionality, hydrophilicity, size, charge, shape, surface chemistry, and many other chemical and physical parameters, different types of cells in the central nervous system can be monitored, modulated, or further studies to elucidate underlying disease mechanisms. Scientists and clinicians have better understood the underlying processes of pathologies for many neurologically related diseases and injuries by implementing multi-dimensional 0D, 1D, and 2D theragnostic nanomaterials. The incorporation of nanomaterials has allowed scientists to better understand how to detect and treat these conditions at an early stage. To this end, having the multi-modal ability to both sense and treat ailments of the central nervous system can lead to favorable outcomes for patients suffering from such injuries and diseases.

Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs.

Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including disc herniation and spinal stenosis. While traditional growth factor therapies (e.g., TGFß) are effective at transiently reversing degenerated disc by stimulation of matrix synthesis, it is increasingly accepted that bioscaffolds are required for sustained, complete IVD regeneration. Current scaffolds (e.g., metal/polymer composites, non-mammalian biopolymers) can be improved in one or more IVD regeneration demands: biodegradability, noninvasive injection, recapitulated healthy IVD biomechanics, predictable crosslinking, and matrix repair induction. To meet these demands, tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel (BIOGEL). The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min, allowing a human operator to easily inject the therapeutic constructs into degenerated IVD. Moreover, BIOGEL encapsulation of TGFß potentiated histological repair (e.g., tissue architecture and matrix synthesis) and functional recovery (e.g., high water retention by promoting the matrix synthesis and reduced pain) in an in vivo rat IVD degeneration/nucleotomy model. This BIOGEL procedure readily integrates into existing nucleotomy procedures, indicating that clinical adoption should proceed with minimal difficulty. Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules, our developed material platform can be extended to other payloads and degenerative injuries.

Structurally Defined Water-Soluble Metallofullerene Derivatives towards Biomedical Applications.

Endohedral metallofullerenes (EMFs) are excellent carriers of rare-earth element (REE) ions in biomedical applications because they preclude the release of toxic metal ions. However, existing approaches to synthesize water-soluble EMF derivatives yield mixtures that inhibit precise drug design. Here we report the synthesis of metallobuckytrio (MBT), a three-buckyball system, as a modular platform to develop structurally defined water-soluble EMF derivatives with ligands by choice. Demonstrated with PEG ligands, the resulting water-soluble MBTs show superb biocompatibility. The Gd MBTs exhibit superior T1 relaxivity than typical Gd complexes, potentially superseding current clinical MRI contrast agents in both safety and efficiency. The Lu MBTs generated reactive oxygen species upon light irradiation, showing promise as photosensitizers. With their modular nature to incorporate other ligands, we anticipate the MBT platform to open new paths towards bio-specific REE drugs.