Iodinated gadolinium-gold nanomaterial as a multimodal contrast agent for cartilage tissue imaging.

Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.

Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer.

Gefitinib (GEF) is an FDA-approved anti-cancer drug for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the efficacy of anticancer drugs is limited due to their non-specificity, lower accumulation at target sites, and systemic toxicity. Herein, we successfully synthesized a modified GEF (mGEF) drug and conjugated to Iron oxide nanoparticles (Fe3O4 NPs) for the treatment of NSCLC via magnetic resonance (MR) image-guided drug delivery. A traditional EDC coupling pathway uses mGEF to directly conjugate to Fe3O4 NPs to overcom the drug leakage issues. As a result, we found in vitro drug delivery on mGEF- Fe3O4 NPs exhibits excellent anticancer effects towards the PC9 cells selectively, with an estimated IC 50 value of 2.0 µM. Additionally, in vivo MRI and PET results demonstrate that the NPs could accumulate in tumor-specific regions with localized cell growth inhibition. Results also revealed that outer tumor region exhibiting a stronger contrast than the tinner tumor region which may due necrosis in inner tumor region. In vivo biodistribution further confirms Fe3O4 NPs are more biocompatible and are excreated after the treatment. Overall, we believe that this current strategy of drug modification combined with chemical conjugation on magnetic NPs will lead to improved cancer chemotherapy as well as understanding the tumor microenvironments for better therapeutic outcomes.

Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy.

Dynamic therapies have potential in cancer treatments but have limitations in efficiency and penetration depth. Here a membrane-integrated liposome (MIL) is created to coat titanium dioxide (TiO2) nanoparticles to enhance electron transfer and increase radical production under low-dose X-ray irradiation. The exoelectrogenic Shewanella oneidensis MR-1 microorganism presents an innate capability for extracellular electron transfer (EET). An EET-mimicking photocatalytic system is created by coating the TiO2 nanoparticles with the MIL, which significantly enhances superoxide anions generation under low-dose (1 Gy) X-ray activation. The c-type cytochromes-constructed electron channel in the membrane mimics electron transfer to surrounding oxygen. Moreover, the hole transport in the valence band is also observed for water oxidation to produce hydroxyl radicals. The TiO2@MIL system is demonstrated against orthotopic liver tumours in vivo.

Ligand free FeSn2 alloy nanoparticles for safe T2-weighted MR imaging of in vivo lung tumors.

Biosafety is a critical issue for the successful translocation of nanomaterial-based therapeutic/diagnostic agents from bench to bedside. For instance, after the withdrawal of clinically approved magnetic resonance (MR) imaging contrast agents (CAs) due to their biosafety issues, there is a massive demand for alternative, efficient, and biocompatible MR contrast agents for future MRI clinical applications. To this end, here we successfully demonstrate the in vivo MR contrast abilities and biocompatibilities of ligand-free FeSn2 alloy NPs for tracking in vivo lung tumors. In vitro and in vivo results reveal the FeSn2 alloy NPs acting as appreciable T2 weighted MR contrast agents to locate tumors. The construction of iron (Fe) on biocompatible tin (Sn) greatly facilitates the reduction of the intrinsic toxicities of Fe in vivo resulting in no significant abnormalities in liver and kidney functions. Therefore, we envision that constructing ligand-free alloy NPs will be a promising candidate for tracking in vivo tumors in future clinical applications.

Engineering H2 O2 and O2 Self-Supplying Nanoreactor to Conduct Synergistic Chemiexcited Photodynamic and Calcium-Overloaded Therapy in Orthotopic Hepatic Tumors.

Photodynamic therapy (PDT) is traditionally ineffective for deeply embedded tumors due to the poor penetration depth of the excitation light. Chemiluminescence resonance energy transfer (CRET) has emerged as a promising mode of PDT without external light. To date, related research has frequently used endogenous hydrogen peroxide (H2 O2 ) and oxygen (O2 ) inside the solid tumor microenvironment to trigger CRET-mediated PDT. Unfortunately, this significantly restricts treatment efficacy and the development of further biomedical applications because of the limited amounts of endogenous H2 O2 and O2 . Herein, a nanohybrid (mSiO2 /CaO2 /CPPO/Ce6: mSCCC) nanoparticle (NP) is designed to achieve synergistic CRET-mediated PDT and calcium (Ca2+ )-overload-mediated therapy. The calcium peroxide (CaO2 ) formed inside mesoporous SiO2 (mSC) with the inclusion of the chemiluminescent agent (CPPO) and photosensitizer (Ce6) self-supplies H2 O2 , O2 , and Ca2+ allowing for the subsequent treatments. The Ce6 in mSCCC NPs is excited by chemical energy in situ following the supply of H2 O2 and O2 to produce singlet oxygen (1 O2 ). The nanohybrid NPs are coated with stearic acid to avoid decomposition during blood circulation through contact with aqueous environment. This nanohybrid shows promising performance in the generation of 1 O2 for external light-free PDT and the release of Ca2+ ions for Ca2+ -overloaded therapy against orthotopic hepatocellular carcinoma.

Magnetic, biocompatible FeCO3 nanoparticles for T2-weighted magnetic resonance imaging of in vivo lung tumors.

BACKGROUND: Late diagnosis of lung cancer is one of the leading causes of higher mortality in lung cancer patients worldwide. Significant research attention has focused on the use of magnetic resonance imaging (MRI) based nano contrast agents to efficiently locate cancer tumors for surgical removal or disease diagnostics. Although contrast agents offer significant advantages, further clinical applications require improvements in biocompatibility, biosafety and efficacy. RESULTS: To address these challenges, we fabricated ultra-fine Iron Carbonate Nanoparticles (FeCO3 NPs) for the first time via modified literature method. Synthesized NPs exhibit ultra-fine size (~ 17 nm), good dispersibility and excellent stability in both aqueous and biological media. We evaluated the MR contrast abilities of FeCO3 NPs and observed remarkable T2 weighted MRI contrast in a concentration dependent manner, with a transverse relaxivity (r2) value of 730.9 ± 4.8 mM-1 S-1at 9.4 T. Moreover, the r2 values of present FeCO3 NPs are respectively 1.95 and 2.3 times higher than the clinically approved contrast agents Resovist® and Friedx at same 9.4 T MR scanner. FeCO3 NPs demonstrate an enhanced T2 weighted contrast for in vivo lung tumors within 5 h of post intravenous administration with no apparent systemic toxicity or induction of inflammation observed in in vivo mice models. CONCLUSION: The excellent biocompatibility and T2 weighted contrast abilities of FeCO3 NPs suggest potential for future clinical use in early diagnosis of lung tumors.

Chemical Structure and Shape Enhance MR Imaging-Guided X-ray Therapy Following Marginative Delivery.

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle-vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.

Peroxidase Mimetic Nanozymes in Cancer Phototherapy: Progress and Perspectives.

Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as photodynamic therapy (PDT) and radio therapy (RT), are strongly oxygen-dependent, which hinders their practical applications. Later on, several strategies were developed to overcome tumor hypoxia, such as oxygen carrier nanomaterials and oxygen generated nanomaterials. Among these, oxygen species generation on nanozymes, especially catalase (CAT) mimetic nanozymes, convert endogenous hydrogen peroxide (H2O2) to oxygen (O2) and peroxidase (POD) mimetic nanozymes converts endogenous H2O2 to water (H2O) and reactive oxygen species (ROS) in a hypoxic tumor microenvironment is a fascinating approach. The present review provides a detailed examination of past, present and future perspectives of POD mimetic nanozymes for effective oxygen-dependent cancer phototherapeutics.