The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive ...materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near-infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)⁻Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin⁻PEI⁻Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR-triggerable property that provides local hyperthermic temperature by PEI⁻Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications.
Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to ...modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm.sup.- 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways. These findings suggest that the engineered GelAlg@rGO-pEV hydrogel has the potential to serve as a wound dressing that can modulate immune responses, inflammation, angiogenesis, and follicle regeneration in diabetic wounds, potentially leading to accelerated healing of chronic wounds.
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•Biomimetic photothermal platelets-polypyrrole (PPY) nanomaterial for drug-free targeted lung cancer photothermal treatment.•In vitro and in vivo accumulation in lung cancer cells ...through epidermal growth factor receptor-mediated cancer cellular endocytosis.•In vivo, the platelets-nanoparticles trick the innate macrophage identification system to prolong retention times and enhance therapeutic efficacy.•Facilitated targeted ablation by photothermally responsive platelets-PPY nanoparticles under near-infrared irradiation.
Platelets have unique properties that can be used in a variety of clinical settings. Their ability to target and accumulate in the lung cancer microenvironment can be exploited as a therapeutic targeted delivery method. In this study, we developed a drug-free biomimetic platelet-polyethyleneimine polypyrrole (PLT-PEI-PPY) conjugate that expresses epidermal growth factor (EGF) as a novel receptor-mediated material for efficient photothermal near-infrared (NIR) irradiation-hyperthermia and lung tumor ablation therapy. A neutral charge, photothermal response, and serum stability were discovered to be unique physiochemical features of this material. The PLT-PEI-PPY nanoparticles selectively aggregated in lung cancer cells in vitro and in vivo and had an anticancer impact via EGF receptor-mediated cancer cell endocytosis. In vivo, systemic injection of the platelet-PPY nanomaterial into mice was found to be safe and could fool the innate macrophage recognition system allowing to extend the residence time, and to improve the distribution to lung tumor tissues and the photothermal therapeutic efficacy under NIR illumination. By attaching photothermally responsive PEI-PPY nanoparticles to platelet membranes and exposing them to NIR irradiation, targeted ablation of lung malignancies was made possible. This nanoformulation, free of hazardous anticancer drugs, demonstrated a safer and more-effective bio-inspired photothermal-driven ablation therapy for lung cancer.
Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis ...fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.
Curcumin can reduce the production of brain inflammatory mediators and symptoms of brain diseases. However, a large amount of free curcumin needs to be administered to achieve an effective level in ...the brain because of its poor water-solubility. Fucoidan and chitosan were reported to respectively target P-selectin and acidic microenvironment expressed by pathologically inflammatory cells/tissues. Herein, the self-assembly of chitosan and fucoidan which could encapsulate curcumin was developed to form the multi-stimuli-responsive nanocarriers, and their pathological pH- and P-selectin-responsive aspects were characterized. Through intranasal delivery to the brain, these curcumin-containing chitosan/fucoidan nanocarriers with dual pH-/P-selectin-targeting properties to the brain lesions improved drug delivery, distribution, and accumulation in the inflammatory brain lesions as evidenced by an augmented inhibitory effect against brain inflammation. This promising multifunctional nanocarrier with a novel drug-delivery route should allow potential clinical biomedical uses by neurosurgeon in the future.
Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and ...applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration.
Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy.
In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups.
Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.
Nanomaterial mediated cancer/tumor photo driven hyperthermia has obtained great awareness. Nevertheless, it is a challenge for improving the hyperthermic efficacy lacking resistance to stimulated ...thermal stress. We thus developed a bioinspired nano-platform utilizing inclusion complexation between photosensitive polypyrrole (Ppy) nanoparticles (NP) and fucoidan (FU). This FU-Ppy NP proved to be an excellent P-selectin-mediated, lung cancer-cell/tumor targeting delivery and specific accumulation, could augment cancer/tumor oxidative stress levels through producing cellular reactive oxygen species. Potent ROS/photothermal combinational therapeutic effects were exhibited by the bioinspired FU-Ppy NP through a selective P-selectin cancer/tumor targeting aptitude for the lung cancer cells/tumor compared with other nano-formulations. The usage of FU-Ppy NP also involves the potential mechanism of suppressing the biological expression of tumor vascular endothelial growth factor (VEGF). This FU biological macromolecule-amplified photothermally therapeutic nano-platform has promising potential for future medical translation in eradicating numerous tumors.
Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their ...efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.
•Fu-MoS2 NMs coated urine tube matrix was made by plasma technique.•This Fu-MoS2 NMs-coated urine tube matrix was analyzed.•This proposed development is expected for medical devices for clinical use.
...The primary barriers preventing the use of silicone-based catheters in medicine, especially for long-term indwelling, are bacterial-related illnesses, blood clotting, inflammation, and cell and tissue adhesion. To address the challenges related to the use of silicone-based catheters, this study presents a novel approach for developing a facile coating composed of anionic and amphiphilic fucoidan (Fu) and phototherapeutic molybdenum disulfide (MoS2) nanomicelles (Fu-MoS2 NMs) through oxygen plasma irradiation. The coating was consecutively applied to medical-grade silicone-based catheters. In this study, stable polymeric coatings were successfully prepared on previously used silicone rubber substrates through the formation of intermolecular bonds between active functional groups in Fu-MoS2 NMs and the side chains of residues on activated silicone interfaces. This study systematically verified a strong relationship between the composition of Fu-MoS2 NMs and their ability to effectively combat bacterial infections, inflammation, blood coagulation, and cell and tissue adhesion, simultaneously maintaining the biocompatibility of silicone rubber substrates. The findings of this study indicate that this simple yet effective interface design procedure can be readily employed for the development of silicone-based urinary catheters. The proposed strategy can be used for the development of diverse interface functionalization techniques for silicone-based medical devices, thus expanding the range of their medical applications.
Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific ...distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency.
Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.
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