Ultrasmall Prussian Blue Nanozyme Attenuates Osteoarthritis by Scavenging Reactive Oxygen Species and Regulating Macrophage Phenotype.

Osteoarthritis (OA) is a degenerative joint disease characterized by obscure etiology and unsatisfactory therapeutic outcomes, making the development of new efficient therapies urgent. Superfluous reactive oxygen species (ROS) have historically been considered one of the crucial factors inducing the pathological progression of OA. Ultrasmall Prussian blue nanoparticles (USPBNPs), approximately sub-5 nm in size, are developed by regulating the configuration of polyvinylpyrrolidone chains. USPBNPs display an excellent ROS eliminating capacity and catalase-like activity, capable of decomposing hydrogen peroxide (H2O2) into O2. The anti-inflammatory mechanism of USPBNPs can be attributed to repolarizing macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype by decreasing the ROS levels accompanied by O2 improvement. Additionally, USPBNPs exhibit an exciting therapeutic efficiency against OA, comparable to that of hydrocortisone in vivo. This study not only develops a new therapeutic agent for OA but also offers an estimable insight into the application of the nanozyme.

Cobalt doped Prussian blue modified hollow polydopamine for enhanced antibacterial therapy.

Give the emergence of drug resistance in bacteria resulting from antibiotic misuse, there is an urgent need for research and application of novel antibacterial approaches. In recent years, nanoparticles (NPs) have garnered significant attention due to their potential to disrupt bacteria cellular structure through loading drugs and special mechanisms, thus rendering them inactive. In this study, the surface of hollow polydopamine (HPDA) NPs was utilized for the growth of Prussian blue (PB), resulting in the formation of HPDA-PB NPs. Incorporation of Co element during the preparation process led to partial doping of PB with Co2+ions. The performance test results demonstrated that the HPDA-PB NPs exhibited superior photothermal conversion efficiency and peroxidase-like activity compared to PB NPs. HPDA-PB NPs have the ability to catalyze the formation of hydroxyl radicals from H2O2in a weakly acidic environment. Due to the tiny PB particles on the surface and the presence of Co2+doping, they have strong broad-spectrum antibacterial properties. Bothin vitroandin vivoevaluations confirm their efficacy against various bacterial strains, particularlyStaphylococcus aureus, and their potential to promote wound healing, making them a promising candidate for advanced wound care and antimicrobial applications.

In vitro and in vivo removal efficacy of insoluble Prussian blue in combination with calcium polystyrene sulfonate for thallium.

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg-1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg-1, orally, twice a day, PB 3 g kg-1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g-1) as compared to PB (37.771 mg g-1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.

Self-synergistic effect of Prussian blue nanoparticles for cancer therapy: driving photothermal therapy and reducing hyperthermia-induced side effects.

BACKGROUND: Photothermal therapy (PTT), involving application of localized hyperthermia to kill cancer cells, has attracted wide attention in cancer therapy. The production of reactive oxygen species (ROS) during PTT may cause irreversible damage to healthy tissues around the tumor. Simultaneously, hyperthermia can stimulate inflammatory response, thus promoting tumor recurrence and metastasis. Therefore, it is of paramount importance to reduce the undesired side effects for further development of PTT. RESULTS: Using a hydrothermal method, spherical Prussian blue nanoparticles (PBs) with uniform size were prepared. The PBs exhibited good dispersion and stability in saline with an average hydrodynamic size of 110 nm. The prepared PBs had a high photothermal conversion efficiency and photothermal stability. The PBs showed intrinsic ROS scavenging properties in vitro. Antioxidant and anti-inflammatory effects of PBs were also observed in vivo. Assessment of toxicity and endoplasmic reticulum stress-inducing ability showed that PBs did not induce an inflammatory response. Tissues of major organs of mice stained with hematoxylin-eosin showed no significant damage, indicating good biocompatibility and safety of PBs. CONCLUSION: The designed single-component PBs with intrinsic ROS scavenging and anti-inflammatory properties could avoid inflammatory response and heat stress-induced ROS during PTT. Thus, further research on PBs is worthwhile to achieve their clinical translation and promote the development of PTT.

Prussian blue-based theranostics for ameliorating acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment. RESULTS: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin). CONCLUSION: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.

BACKGROUND: Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS: Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION: "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.

In Situ Monitoring of the "Point Discharge" Induced Antibacterial Process by the Onsite Formation of a Raman Probe.

Electroporation induced by the "point discharge" effect is an effective technique for bacteria inactivation. Rapidly monitoring the electroporation-induced inactivation process is important for screening nanomaterials with high antimicrobial performance. In this study, we develop a facile strategy to in situ monitor the electroporation induced antimicrobial mechanism based on the surface-enhanced Raman scattering (SERS) effect of the Au-nanotip arrays. Owning to the high local-electric field (∼107 V m-1) generated on the Au nanotips, the bacteria are rapidly electroporated and effectively inactivated with ≥99.9% reduction in bacteria colony counts by only applying an external voltage of +0.8 V for 10 s. The related inactivation mechanism is directly verified by the formation of the Prussian blue (PB) nanocrystals by leaking of the uptaken [Fe(CN)6]3- ions from the cleavage area on the cell membrane. These [Fe(CN)6]3- ions react with Fe2+ to form PB nanocrystals onsite as soon as they leak out. The characteristic peak of PB in the cellular Raman-silent region provides a collective monitoring approach for the destruction of microorganisms. The present strategy not only develops a facial method for future use in evaluating electroporation materials, but also paves a rapid way for offering accurate information on some antibacterial and antitumor processes.

Hollow Prussian Blue Nanozymes Drive Neuroprotection against Ischemic Stroke via Attenuating Oxidative Stress, Counteracting Inflammation, and Suppressing Cell Apoptosis.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi3+-assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Novel photo-thermally active polyvinyl alcohol-Prussian blue nanoparticles hydrogel films capable of eradicating bacteria and mitigating biofilms.

Antibacterial treatment is an essential issue in many diverse fields, from medical device treatments (for example prostheses coating) to food preservation. However, there is a need of novel and light-weight materials with high antibacterial efficiency (preferably due to the physical activation). Utilization of photo-thermally active nanoparticles can lead to novel and re-usable materials that can be remotely activated on-demand to thermally eradicate bacteria and mitigate biofilm formation, therefore meeting the above challenge. In this study polyvinyl alcohol (PVA) hydrogel films containing non-toxic and highly photo-thermally active Prussian blue (PB) nanoparticles were fabricated. The confocal microscopy studies indicated a uniform nanoparticle distribution and a low degree of aggregation. Upon near-infrared (NIR; 700 and 800 nm) light irradiation of PVA-PB films, the local temperature increases rapidly and reaches a plateau (up to ΔT â‰… 78 °C), within ≈6-10 s under relatively low laser intensities, I â‰… 0.3 W cm-2. The high and localized increase of temperature on the fabricated films resulted in an efficient antibacterial effect on Pseudomonas aeruginosa (P. aeruginosa) bacteria. In addition, the localized photo-thermal effect was also sufficient to substantially mitigate biofilms growth.

Solochrome cyanine: A histological stain for cobalt-chromium wear particles in metal-on-metal periprosthetic tissues.

Metal-on-metal (MoM) hip arthroplasties produce abundant implant-derived wear debris composed mainly of cobalt (Co) and chromium (Cr). Cobalt-chromium (Co-Cr) wear particles are difficult to identify histologically and need to be distinguished from other wear particle types and endogenous components (e.g., haemosiderin, fibrin) which may be present in MoM periprosthetic tissues. In this study we sought to determine whether histological stains that have an affinity for metals are useful in identifying Co-Cr wear debris in MoM periprosthetic tissues. Histological sections of periprosthetic tissue from 30 failed MoM hip arthroplasties were stained with haematoxylin-eosin (HE), Solochrome Cyanine (SC), Solochrome Azurine (SA) and Perls' Prussian Blue (PB). Sections of periprosthetic tissue from 10 cases of non-MoM arthroplasties using other implant biomaterials, including titanium, ceramic, polymethylmethacrylate (PMMA) and ultra-high molecular weight polyethylene (UHMWP) were similarly analysed. Sections of 10 cases of haemosiderin-containing knee tenosynovial giant cell tumour (TSGCT) were also stained with HE, SC, SA and PB. In MoM periprosthetic tissues, SC stained metal debris in phagocytic macrophages and in the superficial necrotic zone which exhibited little or no trichrome staining for fibrin. In non-MoM periprosthetic tissues, UHMWP, PMMA, ceramic and titanium particles were not stained by SC. Prussian Blue, but not SC or SA, stained haemosiderin deposits in MoM periprosthetic tissues and TSGT. Our findings show that SC staining (most likely Cr-associated) is useful in distinguishing Co-Cr wear particles from other metal/non-metal wear particles types in histological preparations of periprosthetic tissue and that SC reliably distinguishes haemosiderin from Co-Cr wear debris.

Porous Prussian Blue Nanocubes as Photothermal Ablation Agents for Efficient Cancer Therapy.

Nanomaterial-based photothermal agents have attracted great attention as near-infrared laser driven ablation agents for tumor therapy. In this work, Prussian blue nanocubes with porous interior were synthesized via controlled chemical etching method and successfully applied for efficient photothermal ablation of tumor cells in vitro. Monodispersed porous Prussian blue nanocubes (115.4±4.7 nm) were produced through a controlled self-etching reaction in the presence of polyvinylpyrrolidone (PVP). Owing to the strong absorbance in near infrared (NIR) region, the resulted porous Prussian blue nanocubes could lead to more than 80% death of Hela cells after being treated with nanocubes of concentration as low as 100 µg mL−1. Compared to the traditional solid Prussian blue nanoparticles, these porous nanocubes can provide extra space for encapsulating anti-cancer drugs in their porous interior. It is anticipated that these porous Prussian blue nanocubes can be applied as an enabling platform to develop the next generation of multifunctional drug carrier for cancer treatments.

Prussian Blue Nanoparticles as Multienzyme Mimetics and Reactive Oxygen Species Scavengers.

The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes.

Comparison of Absorbents and Drugs for Internal Decorporation of Radiocesium: Advances of Polyvinyl Alcohol Hydrogel Microsphere Preparations Containing Magnetite and Prussian Blue.

Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase(®) (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37±0.09) was improved by the hydrogel form (1.52±0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17±0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.

[Application of deactivating properties of some sorbents in aquaculture feed production].

The possibility and effectiveness of application of selective sorbents for fish feed production in aquaculture in the area exposed to the radioactive pollution were studied. The investigations of the fish feed deactivating properties with additives of ferrocyn and potassium alginate, and magnesium on whitefish fry-fingerlings and yearlings were carried out. The study has shown that the ferrocyn performance is greater than 99% regardless of the fish age. 1% ferrocyn addition to feed allows increasing the acceptable concentration of feed compo- nents polluted by the above norm cesium radionuclide up to 20 times. The alginate additives in feed provide almost double decrease in the activity of fish tissues. The optimally effective alginate dose should exceed the calcium concentration in feed up to 4 times. It was found that utilization of the feedstock (fish meal, crops and legumes, oil meal and oil cake) polluted by radionuclides is possible in combined aquaculture feed pro- duction. The application of sorbents in feed will allow increasing the amount permissible for use of the feed components polluted above the norm; ensure the radiation safety of feed and, finally, the protection of aquatic biological resources from radioactive contamination. It is shown that the sorbent additive in feed is also jus- tified in case of fish farming in closed waters affected by radioactive pollution. Feeding by mixed fodder with the sorbent additives prevents fish from radionuclide intake from natural food sources.

Designing Mesoporous Prussian Blue@zinc Phosphate Nanoparticles with Hierarchical Pores for Varisized Guest Delivery and Photothermally-Augmented Chemo-Starvation Therapy.

Background: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy. Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy. Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice. Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors.

Prussian Blue Nanohybridized Multicellular Spheroids as Composite Engraftment for Antioxidant Bone Regeneration and Photoacoustic Tomography.

Regulating the complex microenvironment after tooth extraction to promote alveolar bone regeneration is a pressing challenge for restorative dentistry. In this study, through modulating the mechanical properties of the cellular matrix, we guided various types of cells by self-organizing to form multicellular spheroids (MCSs) and hybridized MCSs with Prussian Blue nanoparticles (PBNPs) in the process. The constructed Prussian Blue nanohybridized multicellular spheroids (PBNPs@MCSs) with empowered antioxidant functions effectively reduced cell apoptosis under peroxidative conditions and exhibited enhanced ability to regulate the microenvironment and promote bone repair both in vitro and in vivo. In addition, the PBNPs@MCSs exhibited enhanced photoacoustic imaging ability to trace low doses of PBNPs. Therefore, the constructed PBNPs@MCSs based on the biomimetic hydrogel can be used as a form of an engraftment building block, with a greater potential for pro-bone repair application in the complex microenvironment of the oral cavity.

Mild-photothermal and nanocatalytic therapy for obesity and associated diseases.

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm2, 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases.

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.

Photothermal therapy co-localized with CD137 agonism improves survival in an SM1 melanoma model without hepatotoxicity.

Aim: We investigate combining Prussian Blue nanoparticles (PBNPs), as photothermal therapy (PTT) agents, with agonistic CD137 antibodies (αCD137) on a single nanoparticle platform to deliver non-toxic, anti-tumor efficacy in SM1 murine melanoma.Methods: We electrostatically coated PBNPs with αCD137 (αCD137-PBNPs) and quantified their physicochemical characteristics, photothermal and co-stimulatory capabilities. Next, we tested the efficacy and hepatotoxicity of PTT using αCD137-PBNPs (αCD137-PBNP-PTT) in SM1 tumor-bearing mice.Results: The αCD137-PBNPs retained both the photothermal and agonistic properties of the PBNPs and αCD137, respectively. In vivo, SM1 tumor-bearing mice treated with αCD137-PBNP-PTT exhibited a significantly higher survival rate (50%) without hepatotoxicity, compared with control treatments.Conclusion: These data suggest the potential utility of co-localizing PBNP-PTT with αCD137-based agonism as a novel combination nanomedicine.

Photothermal therapy is a strategy to kill cancer cells that uses nanoparticles and lasers to generate heat. Here, we combine photothermal therapy with an immunotherapy that activates the body's T cells, a type of white blood cell, on a single platform, to treat melanoma, a type of skin cancer in a mouse. We find that this novel nanoparticle-based platform significantly improves the survival of mice bearing melanoma, without increasing liver toxicity.

Hybrid Hydrogels for Immunoregulation and Proangiogenesis through Mild Heat Stimulation to Accelerate Whole-Process Diabetic Wound Healing.

Intense and persistent oxidative stress, excessive inflammation, and impaired angiogenesis severely hinder diabetic wound healing. Bioactive hydrogel dressings with immunoregulatory and proangiogenic properties have great promise in treating diabetic wounds. However, the therapeutic effects of dressings always depend on drugs with side effects, expensive cytokines, and cell therapies. Herein, a novel dynamic borate-bonds crosslinked hybrid multifunctional hydrogel dressings with photothermal properties are developed to regulate the microenvironment of diabetic wound sites and accelerate the whole process of its healing without additional medication. The hydrogel is composed of phenylboronic acid-modified chitosan and hyaluronic acid (HA) crosslinked by tannic acid (TA) through borate bonds and Prussian blue nanoparticles (PBNPs) with photothermal response characteristics are embedded in the polymer networks. The results indicate hydrogels show inherent broad-spectrum antioxidative activities through the integrated interaction of borate bonds, TA, and PBNPs. Meanwhile, combined with the regulation of macrophage phenotype by HA, the inflammatory microenvironment of diabetic wounds is transformed. Moreover, the angiogenesis is then enhanced by the mild photothermal effect of PBNPs, followed by promoted epithelialization and collagen deposition. In summary, this hybrid hydrogel system accelerates all stages of wound repair through antioxidative stress, immunomodulation, and proangiogenesis, showing great potential applications in diabetic wound management.