Dermal extracellular matrix gelatin delivering Prussian blue nanoparticles to relieve skin flap ischemia.

The survival rate of flap is a crucial factor for determining the success of tissue repair and reconstruction. Flap transplantation surgery often leads to ischemic and reperfusion injury, causing apoptosis and tissue necrosis, which significantly reduces the survival rate of flap. To address this issue, we developed a porcine skin decellularized matrix gel nanocomplex loaded with alprostadil (Alp) in Prussian blue nanoparticles (PB NPs) called Alp@PB-Gel. This gel not only maintained the cell affinity of the extracellular scaffold but also exhibited a high degree of plasticity. In vitro assays demonstrated that Alp@PB-Gel possessed antioxidant activity, scavenging ROS ability, and effectively promoted the angiogenesis and migration of human vascular endothelial cells (HUVECs) by stimulating the proliferation of vascular epithelial cells and fibroblasts. In vivo assays further confirmed that Alp@PB-Gel could effectively alleviate necrosis in the early and late stages after surgery, downregulate the levels of NLRP3 and CD68 to inhibit apoptosis and attenuate inflammation, while upregulate the levels of VEGF and CD31 to promote vascular tissue regeneration. Moreover, Alp@PB-Gel exhibited excellent cell affinity and biocompatibility, highlighting its potential for clinical application.

Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy.

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.

Colorimetric and Electrochemical Dual-Mode Detection of Thioredoxin 1 Based on the Efficient Peroxidase-Mimicking and Electrocatalytic Property of Prussian Blue Nanoparticles.

As a potent detection method for cancer biomarkers in physiological fluid, a colorimetric and electrochemical dual-mode sensing platform for breast cancer biomarker thioredoxin 1 (TRX1) was developed based on the excellent peroxidase-mimicking and electrocatalytic property of Prussian blue nanoparticles (PBNPs). PBNPs were hydrothermally synthesized using K3[Fe(CN)6] as a precursor and polyvinylpyrrolidone (PVP) as a capping agent. The synthesized spherical PBNPs showed a significant peroxidase-like activity, having approximately 20 and 60% lower Km values for 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, respectively, compared to those of horseradish peroxidase (HRP). The PBNPs also enhanced the electron transfer on the electrode surface. Based on the beneficial features, PBNPs were used to detect target TRX1 via sandwich-type immunoassay procedures. Using the strategies, TRX1 was selectively and sensitively detected, yielding limit of detection (LOD) values as low as 9.0 and 6.5 ng mL-1 via colorimetric and electrochemical approaches, respectively, with a linear range of 10-50 ng mL-1 in both strategies. The PBNP-based TRX1 immunoassays also exhibited a high degree of precision when applied to real human serum samples, demonstrating significant potentials to replace conventional HRP-based immunoassay systems into rapid, robust, reliable, and convenient dual-mode assay systems which can be widely utilized for the identification of important target molecules including cancer biomarkers.

Immunotherapy of M2 macrophage derived from exosome-based nanoparticles for spinal cord injury.

Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H2O2-induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible.

A NiFe PBA/AuNPs nanocomposite sensitive immunosensor for electrochemical detection of PSA.

In this paper, a label-free electrochemical immunosensor for sensitive detection of prostate antigen (PSA) was developed based on a NiFe PBA/AuNPs composite. The prostate antigen antibody was immobilized and the immunosensor was constructed by using a glassy carbon electrode modified with a nanocomposite consisting of nickel-iron Prussian blue analog (NiFe PBA) and gold nanoparticles (AuNPs). Due to the good biological affinity of AuNPs for biomolecules, as well as the porous nanostructure and regular shape of NiFe PBA, NiFe PBA/AuNPs nanocomposites significantly improve the electron transport rate, while achieving excellent performance for the sensor. Due to the interaction between the antibody and the antigen on the modified electrode, the current signal of the NiFe PBA itself is reduced due to the redox changes in Fe2+ and Fe3+, which can be determined by differential pulse voltammetry (DPV). Therefore, the monitoring of prostate antigen detection is realized. Under optimal experimental conditions, the immunosensor exhibited excellent detection performance with a dynamic response range from 0.5 pg mL-1 to 1000 pg mL-1 for the PSA concentration and a detection limit of 0.23 pg mL-1 (S/N = 3). In addition, the PSA aptasensor has good selectivity, high stability, and satisfactory reproducibility and has broad potential in clinical research and diagnostic applications.

Iron overload promotes hemochromatosis-associated osteoarthritis via the mTORC1-p70S6K/4E-BP1 pathway.

BACKGROUNDS: Joint iron overload in hemochromatosis induces M1 polarization in synovial macrophages, releasing pro-inflammatory factors and leading to osteoarthritis development. However, the mechanism by which iron overload regulates M1 polarization remains unclear. This study aims to elucidate the mechanism by which synovial iron overload promotes macrophage M1 polarization. METHODS: In vitro, RAW264.7 macrophages were treated with iron and divided into five groups based on the concentration of the iron chelator, desferrioxamine (DFO): Ctrl, Fe, DFO1, DFO2, and DFO3. In vivo, rats were categorized into five groups based on iron overload and intra-articular DFO injection: A-Ctrl, A-Fe, A-DFO1, A-DFO2, and A-DFO3. Osteoarthritis was induced by transecting the left knee anterior cruciate ligament. Macrophage morphology was observed; Prussian Blue staining quantified iron deposition in macrophages, synovium, and liver; serum iron concentration was measured using the ferrozine method; cartilage damage was assessed using H&E and Safranin O-Fast Green staining; qPCR detected iNOS and Arg-1 expression; Western Blot analyzed the protein expression of iNOS, Arg-1, 4E-BP1, phosphorylated 4E-BP1, p70S6K, and phosphorylated p70S6K; ELISA measured TNF-α and IL-6 concentrations in supernatants; and immunohistochemistry examined the protein expression of F4/80, iNOS, Arg-1, 4E-BP1, phosphorylated 4E-BP1, p70S6K, and phosphorylated p70S6K in the synovium. RESULTS: In vitro, iron-treated macrophages exhibited Prussian Blue staining indicative of iron overload and morphological changes towards M1 polarization. qPCR and Western Blot revealed increased expression of the M1 polarization markers iNOS and its protein. ELISA showed elevated TNF-α and IL-6 levels in supernatants. In vivo, ferrozine assay indicated significantly increased serum iron concentrations in all groups except A-Ctrl; Prussian Blue staining showed increased liver iron deposition in all groups except A-Ctrl. Iron deposition in rat synovium decreased in a DFO concentration-dependent manner; immunohistochemistry showed a corresponding decrease in iNOS and phosphorylated 4E-BP1 expression, and an increase in Arg-1 expression. CONCLUSION: Intracellular iron overload may exacerbate joint cartilage damage by promoting synovial macrophage M1 polarization through phosphorylation of 4E-BP1 in the mTORC1-p70S6K/4E-BP1 pathway.

Disposable label-free electrochemical immunosensor based on gold nanoparticles-Prussian blue for neutrophil gelatinase-associated lipocalin detection in urine samples.

Neutrophil gelatinase-associated lipocalin (NGAL) is a remarkable biomarker for assessing acute kidney injury. In this study, we developed a novel label-free NGAL electrochemical immunosensor based on gold nanoparticles (AuNPs) and Prussian blue (PB) without an external mediator. The AuNPs-PB based immunosensor was fabricated on a custom gold-electrode (AuE)-based polypropylene (PP) substrate. We systematically assessed and optimized key experimental parameters, including the process of AuNPs-PB electrodeposition, antibody concentration, and incubation time. The immunosensor response toward NGAL was determined using differential pulse voltammetry, where the decrease in the oxidation current response of the PB redox probe correlating with the increase in NGAL concentration. Our results demonstrated that the synergistic benefits of both AuNPs and PB significantly improved electrochemical activity for NGAL detection and provided a highly stable sensor across a range of pH values. The label-free immunosensor exhibited two linear ranges: 0.10-1.40 ng mL-1 and 1.40-25.0 ng mL-1, with a low detection limit of 0.094 ng mL-1. The developed NGAL immunosensor displayed high selectivity and excellent reproducibility. Furthermore, NGAL detection was completed within 30 min and the immunosensor exhibited storage stability for six weeks. Notably, NGAL levels determined in human urine samples using this developed label-free immunosensor showed good agreement with the results obtained from the enzyme-linked immunosorbent assay. This novel label-free NGAL immunosensor provides great potential in developing NGAL point-of-care testing applications.

Effects and mechanisms of prussian blue nanozymes with multiple enzyme activities on nasopharyngeal carcinoma cells.

Prussian blue nanozymes (PBNs) with multiple enzyme activities are prepared and their activities of antitumor in nasopharyngeal carcinoma cells (CEN2) are also explored in this research. On the one hand, it shows that PBNs can exert the catalase-like (CAT-like) activity to decompose hydrogen peroxide (H2O2) into non-toxic H2O in CEN2 cells. The O2 release of H2O2 catalysed by PBNs effectively alleviates the hypoxic environment of tumors, which inhibits the glycolysis of tumor and reduces the production of lactic acid. On the other hand, we also find that PBNs also has peroxidase-like (POD-like) enzymatic activity, which can catalyze the production of·OH from H2O2 in tumor cells and result in tumor cell apoptosis. This study lays a solid biomedical foundation for the development of safe and non-toxic nanozymes, as well as the expansion of their application in tumor treatment.

Dual-drug delivery by thermo-responsive Janus nanogel for improved cellular uptake, sustained release, and combination chemo-thermal therapy.

The goal of this work was to examine the heat-sensitizing effects of Janus-coated magnetic nanoparticles (JMNPs) as a vehicle for 5-fluorouracil (5-Fu) and Quercetin (Qu) in C6 and OLN-93 cell lines. The cellular uptake of nanoparticles was evaluated using Prussian blue staining and ICP-OES after monolayer culturing of C6 (rat brain cancer cell) and OLN-93 (normal rat brain cell) cells. The cells were treated with free 5-Fu, Qu, and MJNPs loaded with Qu/5-Fu for 24 h, followed by magnetic hyperthermia under an alternating magnetic field (AMF) at a temperature of 43 °C. Using the MTT test and Flow cytometry, the C6 and OLN-93 cells were investigated after being subjected to hyperthermia with and without magnetic nanoparticles. The results of Prussian blue staining confirmed the potential of MJNPs as carriers that facilitate the uptake of drugs by cancer cells. The results showed that the combined application of Qu/5-Fu/MJNPs with hyperthermia significantly increased the amount of ROS production compared to interventions without MJNPs. The therapeutic results demonstrated that the combination of Qu/5-Fu/MJNPs with hyperthermia considerably enhanced the rate of apoptotic and necrotic cell death compared to that of interventions without MJNPs. Furthermore, MTT findings indicated that controlled exposure of Qu/5-Fu/MJNPs to AMF caused a synergistic effect. The advanced Janus magnetic nanoparticles in this study can be proposed as a promising dual drug carrier (Qu/5-Fu) and thermosensitizer platform for dual-modal synergistic cancer therapy.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

Purpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

Bufotalin-loaded biomimetic Prussian blue nanoparticles for colorectal cancer chemo-photothermal ferroptosis therapy.

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte-tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis.

Structural features of Prussian Blue-related iron complex - FeT of activity to peroxidate unsaturated fatty acids.

Aim: FeT is a complex of Fe3+, ferricyanide and tartrate, similar in structure to Prussian Blue. Its synthesis was planned to produce a potential antiproliferative drug. Methods: Dynamic light scattering was applied to study nanostructures formed by FeT complexes, while their biological activity was tested following changes in cell proliferation using cultured T24 human bladder cancer cells. Results: The antiproliferative activity of FeT derived from its ability to peroxidate unsaturated fatty acids, which can cause cell death through oxidative stress and/or ferroptosis. FeT molecules associate into drop-like nanostructures in water solutions, between 10-130 nm, which can bind albumin. Conclusion: Fatty acid peroxidation is significantly activated by light. The characteristics and reactivity of FeT represent a prospective application in medicine.

Nanosized Prussian blue and its analogs for bioimaging and cancer theranostics.

Prussian blue (PB) nanoparticles (NPs) and Prussian blue analogs (PBAs) can form metal-organic frameworks through the programmable coordination of ferrous ions with cyanide. PB and PBAs represent a burgeoning class of hybrid functional nano-systems with a wide-ranging application spectrum encompassing biomedicine, cancer diagnosis, and therapy. A comprehensive overview of recent advancements is crucial for gaining insights for future research. In this context, we reviewed the synthesis techniques and surface modification strategies employed to tailor the dimensions, morphology, and attributes of PB NPs. Subsequently, we explored advanced biomedical utilities of PB NPs, encompassing photoacoustic imaging, magnetic resonance imaging, ultrasound (US) imaging, and multimodal imaging. In particular, the application of PB NPs-mediated photothermal therapy, photodynamic therapy, and chemodynamic therapy to cancer treatment was reviewed. Based on the literature, we envision an evolving trajectory wherein the future of Prussian blue-driven biological applications converge into an integrated theranostic platform, seamlessly amalgamating bioimaging and cancer therapy. STATEMENT OF SIGNIFICANCE: Prussian blue, an FDA-approved coordinative pigment with a centuries-long legacy, has paved the way for Prussian blue nanoparticles (PB NPs), renowned for their remarkable biocompatibility and biosafety. These PB NPs have found their niche in biomedicine, playing crucial roles in both diagnostics and therapeutic applications. The comprehensive review goes beyond PB NP-based cancer therapy. Alongside in-depth coverage of PB NP synthesis and surface modifications, the review delves into their cutting-edge applications in the realm of biomedical imaging, encompassing techniques such as photoacoustic imaging, magnetic resonance imaging, ultrasound imaging, and multimodal imaging.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination.

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

A copper-platinum nanoplatform for synergistic photothermal and chemodynamic tumor therapy via ROS outburst and GSH exhaustion.

A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.

Red cell membrane-coating Prussian blue for combined photothermal and NO gas therapy for nasopharyngeal carcinoma.

Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading a NO donor (BNN6) onto mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO could also be efficiently released. The generated NO further facilitates the formation of ONOO-, a highly toxic species to tumors, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.

Dual chemodynamic/photothermal therapeutic nanoplatform based on DNA-functionalized prussian blue.

The combination of chemodynamic therapy and photothermal therapy has a promising application owing to its impressive anti-cancer effects. However, the degradability of the material and the lack of targeting severely limit its further clinical application. Herein, DNAs containing nucleolin aptamer (AS1411) and different bases sequences were used to functionalize PB NPs for the targeted treatment. Compared to prussian blue, DNA-functionalized prussian blue does not reduce the photothermal properties of prussian blue. Moreover, DNA confers DNA-functionalized prussian blue targeting and higher enzymatic activity, thereby achieving a more effective combination of chemodynamic and photothermal treatment. The therapeutic efficacy of this nanoplatform was evaluated in vivo and in vitro experiments, exhibiting that DNA-functionalized prussian blue nanozyme can maximize the precise control of the therapeutic effect, reduce the toxic and side effects caused by non-specific accumulation on other normal cells, and effectively achieve targeted killing of cancer cells. This work demonstrates that DNA-functionalized prussian blue can improve the efficiency of combined tumor treatment and enhance the application value of prussian blue in tumor treatment, which is expected to provide theoretical support for clinical application.

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy.

OBJECTIVES: A novel clinically translatable iron oxide nanoparticle (IOP) is currently being tested in phase 2 clinical trials as a magnetic resonance imaging (MRI) contrast agent for hepatocellular carcinoma diagnosis. The purpose of our study is to evaluate if this IOP can detect activation of tumor-associated macrophages (TAMs) due to CD47 mAb-targeted immunotherapy in 2 mouse models of osteosarcoma. MATERIALS AND METHODS: The toxicity, biodistribution, and pharmacokinetics of IOP were evaluated in 77 female and 77 male rats. Then, 24 female BALB/c mice with intratibial murine K7M2 tumors and 24 female NOD scid gamma mice with intratibial human 143B osteosarcoma xenografts were treated with either CD47 mAb (n = 12) or control antibody (n = 12). In each treatment group, 6 mice underwent MRI scans before and after intravenous infusion of either IOP or ferumoxytol (30 mg Fe/kg). Tumor T2* values and TAM markers F4/80, CD80, CD206, and Prussian blue staining were compared between different experimental groups using exact 2-sided Wilcoxon rank sum tests. RESULTS: Biodistribution and safety evaluations of IOP were favorable for doses of less than 50 mg Fe/kg body weight in female and male rats. Both IOP and ferumoxytol caused negative enhancement (darkening) of the tumor tissue. Both murine and human osteosarcoma tumors treated with CD47 mAb demonstrated significantly shortened T2* relaxation times after infusion of IOP or ferumoxytol compared with controls (all P 's < 0.05). Higher levels of F4/80 + CD80 + were found in murine and human osteosarcomas treated with CD47 mAb compared with sham-treated controls (all P 's < 0.05). In addition, murine CD47 mAb-treated tumors after infusion of either IOP or ferumoxytol showed significantly higher numbers of Prussian blue-positive cells compared with controls ( P < 0.05). There was no significant difference of F4/80 + CD206 + cells among any of the groups (all P 's > 0.05). CONCLUSIONS: Iron oxide nanoparticle-enhanced MRI can be used to diagnose CD47 mAb-mediated TAM-activation in osteosarcomas.

Imaging application of an MMP2-sensitive tumor-targeted prussian blue fluorescent nanoprobe.

In recent years, the application of nanoimaging technology on standardize tumor diagnosis has become a new research hotspot, especially nanoprobes. Our research group has synthesized a kind of nanocarrier, mPEG2000-GPLGIAGQ-DSPE, which has the characteristic of matrix metalloproteinase-2 (MMP2) sensitive ability in tumor microenvironment. Meanwhile, the encapsulation method is adopted to prepare MMP2-sensitive tumor-targeted prussian blue fluorescent nanoprobe with mPEG2000-GPLGIAGQ-DSPE as the carrier. On the one hand, this novel nanoprobe not only can effectively improve the solubility of prussian blue, but is non-toxic and safe for cells. On the other hand, octapeptide (GPLGIAGQ) in mPEG2000-GPLGIAGQ-DSPE nanocarrier can specifically respond to MMP2 in tumor cells to release prussian blue, and achieve targeted intelligent imaging of tumor cells.

Design and Development of Fe3O4@Prussian Blue Nanocomposite: Potential Application in the Detoxification of Bilirubin.

BACKGROUND: Prussian blue nanoparticles (PBNPs) due to their high solubility, stability, flexible molecular structure, tunable size, easy synthesis, and surface modification have attracted the attention of researchers as high-efficiency therapeutic agents. Recently, it has been reported that magnetic nanoparticles can be to bind pathogenic substances on their surface, followed by a recollection by magnetic separation. Considering the potential application of PB and magnetic nanoparticles, in the current study we aimed to strategically design and synthesize a highly efficient nano-magnetic bilirubin scavenger system based on iron oxides@prussian blue nanocomposites (Fe3O4@PB) NCs. MATERIALS AND METHODS: The Fe3O4@PB NCs were synthesized by an improved shell-growing procedure and identified using advanced characteristic techniques TEM, SEM, XRD, DLS, and Zeta potential. Synthesized Fe3O4@PB NCs showed good magneton properties and also demonstrated dramatic absorbent properties that empower use as an eco-friendly adsorbent nano agent for the detoxification of toxins. In addition, Fe3O4@PB nanoparticles showed high performance of bilirubin absorption in the serum and blood of sickle cell anemia patients. (Temp. 37.7 ºC, the dose of adsorbent: 1 mg/mL, incubation time 30 min, and initial concentration: 0.25 mg/mL). RESULTS: The results demonstrated an ideal adsorption capacity (86%) of Fe3O4@PB NCs which is significant compared to the reported adsorbents agents. These results pave the way for the application of Fe3O4@PB NCs for the effective purification of toxins from patients' body fluids.