Hybrid Nanoparticles of Extracellular Vesicles and Gemcitabine Prodrug-Loaded Liposomes with Enhanced Targeting Ability for Effective PDAC Treatment.

Liposomes are applied to various anticancer treatments as representative drug delivery carriers. However, liposomes do not have their own targeting properties; therefore, there are limitations in drug delivery to specific tissues or cells. High targetability in drug delivery is an important factor in improving bioavailability and drug efficacy and reducing side effects; recent research has been actively investigated to modify the surface of liposomes to give them specific functions. In this study, we studied a drug delivery system for anticancer treatment that enhances targeting ability through fusion with exosomes on the surface of liposomes. We designed exosome-liposome hybrid nanoparticles loaded with a gemcitabine prodrug as a treatment for pancreatic ductal adenocarcinoma (PDAC). Membrane fusion with exosomes shows excellent targeting ability to pancreatic cancer cells due to intrinsic targeting ability and expansion of the macropinocytosis pathway.

Targeted Liposomal Co-delivery of an Immunogenic Cell Death Inducer and a Toll-Like Receptor 4 Agonist for Enhanced Cancer Chemo-immunotherapy.

Anticancer chemo-immunotherapy has gained considerable attention across various scientific domains as a prospective approach for the comprehensive eradication of malignant tumors. Recent research has particularly been focused on traditional anthracycline chemo drugs, such as doxorubicin and mitoxantrone. These compounds trigger apoptosis in tumor cells and evoke immunogenic cell death (ICD). ICD is a pivotal initiator of the cancer-immunity cycle by facilitating the release of damage-associated molecular patterns (DAMPs). The resultant DAMPs released from cancer cells effectively activate the immune system, resulting in an increase in tumor-infiltrating T cells. In this study, we have innovated a co-delivery strategy involving folate-modified liposomes to deliver doxorubicin and monophosphoryl lipid A (MPLA) simultaneously to tumor tissue. The engineered liposomes exploit the overexpression of folate receptors within the tumor tissues. Delivered doxorubicin initiates ICD at the tumor cells, further enhancing the immunogenic stimulus. Additionally, MPLA helps T cell priming by activating antigen-presenting cells. This intricate interplay culminates in a synergistic effect, ultimately resulting in an augmented and potentiated anticancer chemo-immunotherapeutic liposomal treatment.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

Recent advancements of hydrogels in immunotherapy: Breast cancer treatment.

Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients.

Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells.

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activationmediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells. [BMB Reports 2024; 57(6): 299-304].

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Human archetypal pluripotent stem cells differentiate into trophoblast stem cells via endogenous BMP5/7 induction without transitioning through naive state.

Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGFß), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)-a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.

Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy.

Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 µg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient •OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.

Gene Therapy Using Efficient Direct Lineage Reprogramming Technology for Neurological Diseases.

Gene therapy is an innovative approach in the field of regenerative medicine. This therapy entails the transfer of genetic material into a patient's cells to treat diseases. In particular, gene therapy for neurological diseases has recently achieved significant progress, with numerous studies investigating the use of adeno-associated viruses for the targeted delivery of therapeutic genetic fragments. This approach has potential applications for treating incurable diseases, including paralysis and motor impairment caused by spinal cord injury and Parkinson's disease, and it is characterized by dopaminergic neuron degeneration. Recently, several studies have explored the potential of direct lineage reprogramming (DLR) for treating incurable diseases, and highlighted the advantages of DLR over conventional stem cell therapy. However, application of DLR technology in clinical practice is hindered by its low efficiency compared with cell therapy using stem cell differentiation. To overcome this limitation, researchers have explored various strategies such as the efficiency of DLR. In this study, we focused on innovative strategies, including the use of a nanoporous particle-based gene delivery system to improve the reprogramming efficiency of DLR-induced neurons. We believe that discussing these approaches can facilitate the development of more effective gene therapies for neurological disorders.

Advances in Radionuclides and Radiolabelled Peptides for Cancer Therapeutics.

Radiopharmaceutical therapy, which can detect and treat tumours simultaneously, was introduced more than 80 years ago, and it has changed medical strategies with respect to cancer. Many radioactive radionuclides have been developed, and functional, molecularly modified radiolabelled peptides have been used to produce biomolecules and therapeutics that are vastly utilised in the field of radio medicine. Since the 1990s, they have smoothly transitioned into clinical application, and as of today, a wide variety of radiolabelled radionuclide derivatives have been examined and evaluated in various studies. Advanced technologies, such as conjugation of functional peptides or incorporation of radionuclides into chelating ligands, have been developed for advanced radiopharmaceutical cancer therapy. New radiolabelled conjugates for targeted radiotherapy have been designed to deliver radiation directly to cancer cells with improved specificity and minimal damage to the surrounding normal tissue. The development of new theragnostic radionuclides, which can be used for both imaging and therapy purposes, allows for more precise targeting and monitoring of the treatment response. The increased use of peptide receptor radionuclide therapy (PRRT) is also important in the targeting of specific receptors which are overexpressed in cancer cells. In this review, we provide insights into the development of radionuclides and functional radiolabelled peptides, give a brief background, and describe their transition into clinical application.

Thermosusceptible Nitric-Oxide-Releasing Nitrogel for Strengthening Antitumor Immune Responses with Tumor Collagen Diminution and Deep Tissue Delivery during NIR Laser-Assisted Photoimmunotherapy.

Combined cancer immunotherapy has demonstrated promising potential with an amplified antitumor response and immunosuppressive tumor microenvironment (TME) modulation. However, one of the main issues that cause treatment failure is the poor diffusion and insufficient penetration of therapeutic and immunomodulatory agents in solid tumors. Herein, a cancer treatment approach that combines photothermal therapy (PTT) and nitric oxide (NO) gas therapy for tumor extracellular matrix (ECM) degradation, along with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor that reduces tryptophan catabolism to kynurenine, and DMXAA, a stimulator of interferon gene (STING) agonist that stimulates antigen cross-presentation, is proposed to overcome this issue. Upon NIR (808 nm) laser irradiation, NO-GEL achieved the desired thermal ablation by releasing sufficient tumor antigens through immunogenic cell death (ICD). NO delivery triggered local diffusion of excess NO gas for effectively degrading tumor collagen in the ECM, homogeneously delivered NLG919 throughout the tumor tissue, inhibited IDO expression that was upregulated by PTT, and reduced the immune suppressive activities. The sustained release of DMXAA prolonged dendritic cell maturation and CD8+ T cell activation against the tumor. In summary, NO-GEL therapeutics offer a significant tumor regression with PTT and STING agonist combination that stimulates a durable antitumor immune response. Additional unification of IDO inhibition during PTT supplements the immunotherapy by reducing the T cell apoptosis and immune suppressive cell infiltration to TME. NO-GEL with the STING agonist and IDO inhibitor is an effective therapeutic combination to counter possible limitations during solid tumor immunotherapy.

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis.

The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site. Further, the BIM nanoparticle treatment reduced the influx of macrophages and neutrophils in the injured region by blocking migration and inducing reverse migration in the zebrafish larva tail amputation model as well as in MSU-induced peritonitis and air pouch mouse models. Overall, the current strategy of employing biomineralized nanoscavengers for arthritis demonstrates clinical significance in dual blocking of peroxides and COX2 to prevent influx of inflammatory cells into the sites of inflammation.

Next-Generation 3D Scaffolds for Nano-Based Chemotherapeutics Delivery and Cancer Treatment.

Cancer is the leading cause of death after cardiovascular disease. Despite significant advances in cancer research over the past few decades, it is almost impossible to cure end-stage cancer patients and bring them to remission. Adverse effects of chemotherapy are mainly caused by the accumulation of chemotherapeutic agents in normal tissues, and drug resistance hinders the potential therapeutic effects and curing of this disease. New drug formulations need to be developed to overcome these problems and increase the therapeutic index of chemotherapeutics. As a chemotherapeutic delivery platform, three-dimensional (3D) scaffolds are an up-and-coming option because they can respond to biological factors, modify their properties accordingly, and promote site-specific chemotherapeutic deliveries in a sustainable and controlled release manner. This review paper focuses on the features and applications of the variety of 3D scaffold-based nano-delivery systems that could be used to improve local cancer therapy by selectively delivering chemotherapeutics to the target sites in future.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Magnetofluoro-Immunosensing Platform Based on Binary Nanoparticle-Decorated Graphene for Detection of Cancer Cell-Derived Exosomes.

Multi-functionalized carbon nanomaterials have attracted interest owing to their excellent synergic properties, such as plasmon resonance energy transfer and surface-enhanced Raman scattering. Particularly, nanoparticle (NP)-decorated graphene (GRP) has been applied in various fields. In this study, silver NP (AgNP)- and magnetic iron oxide NP (IONP)-decorated GRP were prepared and utilized as biosensing platforms. In this case, AgNPs and GRP exhibit plasmonic properties, whereas IONPs exhibit magnetic properties; therefore, this hybrid nanomaterial could function as a magnetoplasmonic substrate for the magnetofluoro-immunosensing (MFI) system. Conversely, exosomes were recently considered high-potential biomarkers for the diagnosis of diseases. However, exosome diagnostic use requires complex isolation and purification methods. Nevertheless, we successfully detected a prostate-cancer-cell-derived exosome (PC-exosome) from non-purified exosomes in a culture media sample using Ag/IO-GRP and dye-tetraspanin antibodies (Ab). First, the anti-prostate-specific antigen was immobilized on the Ag/IO-GRP and it could isolate the PC-exosome from the sample via an external magnetic force. Dye-tetraspanin Ab was added to the sample to induce the sandwich structure. Based on the number of exosomes, the fluorescence intensity from the dye varied and the system exhibited highly sensitive and selective performance. Consequently, these hybrid materials exhibited excellent potential for biosensing platforms.

Graphene: A Promising Theranostic Agent.

Graphene has drawn tremendous interest in the field of nanoscience as a superior theranostic agent owing to its high photostability, aqueous solubility, and low toxicity. This monoatomic thick building block of a carbon allotrope exhibits zero to two-dimensional characteristics with a unique size range within the nanoscale. Their high biocompatibility, quantum yield, and photoluminescent properties make them more demandable in biomedical research. Its application in biomedical sciences has been limited due to its small-scale production. Large-scale production with an easy synthesis process is urgently required to overcome the problem associated with its translational application. Despite all possible drawbacks, the graphene-based drug/gene delivery system is gaining popularity day by day. To date, various studies suggested its application as a theranostic agent for target-specific delivery of chemotherapeutics or antibiotics against various diseases like cancer, Alzheimer's diseases, multidrug resistance diseases, and more. Also, studying the toxicological profile of graphene derivatives is very important before starting its practical use in clinical applications. This chapter has tried to abbreviate several methods and their possible incoming perspective as claimed by researchers for mass production and amplifying graphene-based treatment approaches.

Graphene as Photothermal Therapeutic Agents.

Light-assisted hyperthermic therapy is a promising strategy to treat cancer. Graphene and their derivatives with unique physiochemical properties, intrinsic near infrared absorption, and ability to transduce the absorbed light energy into heat, have attracted researchers to use them for photothermal therapy (PTT). In addition, the presence of surface functional groups and large surface area that can facilitate interactions with hydrophobic molecules has favored the use of graphene allotropes for developing PTT-based combinatorial therapies. In this book chapter we have reviewed different graphene-based PTT-assisted photodynamic, gene, chemo, and immunotherapeutic strategies developed to improve the outcome of cancer treatment. We have also discussed how PTT from graphene derivatives can improve the therapeutic outcomes of gene, chemo, and immunotherapies. Finally, this book chapter provides promising insights to develop novel graphene-based multifunctional PTT-assisted combinatorial therapeutics with both imaging and therapeutic regimens to treat cancer.

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy.

Long-term dynamic tracking of cells with theranostic properties remains challenging due to the difficulty in preparing and delivering drugs by probes. Herein, we developed highly fluorescent one- and two-photon (OP and TP) excitable polyphenolic carbon quantum dots (CQDs) for excellent membrane-targeting and drug delivery properties for synergistic tumor therapy. The green-emissive CQDs (g-CQDs) were synthesized from a three-fold symmetric polyphenolic molecule, phloroglucinol (C3h; symmetry elements: E, C3, C32, σh, S3, and S3-1), in a sulfuric acid medium. Doxorubicin (Dox) was loaded onto the g-CQDs via electrostatic interaction, resulting in a loading efficiency and content of 54.62% and 323.25 µg mL-1, respectively. The g-CQDs@Dox complex exhibited a higher rate of cell killing efficiency at both pH 5.0 and 6.5, with higher reactive oxygen species (ROS) generation due to the greater Dox accumulation in the tumor cells. In addition, TP cell imaging displayed excellent membrane-targeting properties with less photobleaching ability in tumor cells. The in vivo studies confirmed that the g-CQDs@Dox complex has higher affinity towards tumor cells, better inhibitory effects, and an absence of systemic toxicity. Therefore, our developed nanocarrier exhibited better cell imaging, drug delivery, and tumor-targeting properties, and could be used as a "smart" probe for synergistic tumor therapy.

Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages.

Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of circulating leukocytes, including neutrophils and monocytes. A key component that aggravates the systemic inflammatory response is the generation of stable reactive oxygen species such as hydrogen peroxide (H2O2). In this study, we present a versatile strategy to reduce the activation of tissue-resident macrophages and prevent leukocyte infiltration in an LPS-induced endotoxemia model. We designed and synthesized hyaluronic acid-stabilized Prussian blue (HAPB) nanoparticles and validated their activity in the dismutation of H2O2 in LPS-induced tissue-resident macrophages. Hyaluronic acid provided stability and enhanced the intracellular uptake of insoluble Prussian blue via the CD44 receptor on LPS-activated macrophages. Following HAPB administration to an LPS-induced peritonitis murine model, the level of M1 inflammatory macrophage population decreased, and the infiltration of neutrophils along with monocytes was suppressed. Overall, we have developed biocompatible Prussian blue nanoparticles to ameliorate inflammatory stress in LPS-induced endotoxemia by scavenging the intracellular peroxide thereby inhibiting inflammatory cascade in tissue-resident macrophages. Therefore, HAPB nanoparticles may potentially be used as novel nano-stress relievers in sepsis. The nanomaterials may have clinical application in sepsis and in other inflammatory diseases involving peroxides as key inflammatory agents.