Spiky Silver-Iron Oxide Nanohybrid for Effective Dual-Imaging and Synergistic Thermo-Chemotherapy.

Nanophotothermal therapy based on nanoparticles (NPs) that convert near-infrared (NIR) light to generate heat to selectively kill cancer cells has attracted immense interest due to its high efficacy and being free of ionizing radiation damage. Here, for the first time, we have designed a novel nanohybrid, silver-iron oxide NP (AgIONP), which was successfully tuned for strong absorbance at NIR wavelengths to be effective in photothermal treatment and dual-imaging strategy using MRI and photoacoustic imaging (PAI) in a cancer model in vivo and in vitro, respectively. We strategically combine the inherent anticancer activity of silver and photothermal therapy to render excellent therapeutic capability of AgIONPs. In vitro phantoms and in vivo imaging studies displayed preferential uptake of folate-targeted NPs in a cancer mice model, indicating the selective targeting efficiency of NPs. Importantly, a single intravenous injection of NPs in a cancer mice model resulted in significant tumor reduction, and photothermal laser resulted in a further substantial synergistic decrease in tumor size. Additionally, biosafety and biochemical assessment performed in mice displayed no significant difference between NP treatment and control groups. Overall, our folic acid AgIONPs displayed excellent potential in the simultaneous application for safe and successful targeted synergistic photothermal treatment and imaging of a cancer model.

Advances in haemostatic sponges: Characteristics and the underlying mechanisms for rapid haemostasis.

In traumatized patients, the primary cause of mortality is uncontrollable continuous bleeding and unexpected intraoperative bleeding which is likely to increase the risk of complications and surgical failure. High expansion sponges are effective clinical practice for the treatment of wound bleeding (irregular/deep/narrow) that are caused by capillaries, veins and even arterioles as they possess a high liquid absorption ratio so can absorb blood platelets easily in comparison with traditional haemostasis treatments, which involve compression, ligation, or electrical coagulation etc. When in contact with blood, haemostatic sponges can cause platelet adhesion, aggregation, and thrombosis, preventing blood from flowing out from wounds, triggering the release of coagulation factors, causing the blood to form a stable polymerized fibre protein, forming blood clots, and achieving the goal of wound bleeding control. Haemostatic sponges are found in a variety of shapes and sizes. The aim of this review is to facilitate an overview of recent research around haemostatic sponge materials, products, and technology. This paper reviews the synthesis, properties, and characteristics of haemostatic sponges, together with the haemostasis mechanisms of haemostatic sponges (composite materials), such as chitosan, cellulose, gelatin, starch, graphene oxide, hyaluronic acid, alginate, polyethylene glycol, silk fibroin, synthetic polymers silver nanoparticles, zinc oxide nanoparticles, mesoporous silica nanoparticles, and silica nanoparticles. Also, this paper reviews commercial sponges and their properties. In addition to this, we discuss various in-vitro/in-vivo approaches for the evaluation of the effect of sponges on haemostasis.

Atherothrombosis-on-Chip: A Site-Specific Microfluidic Model for Thrombus Formation and Drug Discovery.

Atherothrombosis, an atherosclerotic plaque disruption condition with superimposed thrombosis, is the underlying cause of cardiovascular episodes. Herein, a unique design is presented to develop a microfluidic site-specific atherothrombosis-on-chip model, providing a universal platform for studying the crosstalk between blood cells and plaque components. The device consists of two interconnected microchannels, namely main and supporting channels: the former mimics the vessel geometry with different stenosis, and the latter introduces plaque components to the circulation simultaneously. The unique design allows the site-specific introduction of plaque components in stenosed channels ranging from 0% to above 50%, resulting in thrombosis, which has not been achieved previously. The device successfully explains the correlation between vessel geometry and thrombus formation phenomenon as well as the influence of shear rate on platelet aggregation, confirming the reliability and the effectiveness of the design. The device exhibits significant sensitivity to aspirin. In therapeutic doses (50 × 10-6 and 100 × 10-6 m), aspirin delays and prevents platelet adhesion, thereby reducing the thrombus area in a dose-dependent manner. Finally, the device is effectively employed in testing the targeted binding of the RGD (arginyl-glycyl-aspartic acid) labeled polymeric nanoparticles on the thrombus, extending the use of the device to examine targeted drug carriers.

Engineering chitosan nano-cocktail containing iron oxide and ceria: A two-in-one approach for treatment of inflammatory diseases and tracking of material delivery.

In this study, modular two-in-one nano-cocktails were synthesised to provide treatment of inflammatory diseases and also enable tracking of their delivery to the disease sites. Chitosan nano-cocktails loaded with treatment module (cerium oxide nanoparticles) and imaging module (iron oxide nanoparticles) were synthesised by electrostatic self-assembly (Chit-IOCO) and ionic gelation method (Chit-TPP-IOCO), respectively. Their MRI capability, anti-inflammatory and anti-fibrosis ability were investigated. Results demonstrated that Chit-IOCO significantly reduced the expression of TNF-α and COX-2, while Chit-TPP-IOCO reduced IL-6 in the LPS-stimulated macrophages RAW264.7. Cytotoxicity studies showed that the nano-cocktails inhibited the proliferation of macrophages. Additionally, Chit-IOCO exhibited higher in vitro MRI relaxivity than Chit-TPP-IOCO, indicating that Chit-IOCO is a better MRI contrast agent in macrophages. It was possible to track the delivery of Chit-IOCO to the inflamed livers of CCl4-treated C57BL/6 mice, demonstrated by a shortened T2⁎ relaxation time of the livers after injecting Chit-IOCO into mice. In vivo anti-inflammatory and blood tests demonstrated that Chit-IOCO reduced inflammation-related proteins (TNF-a, iNOS and Cox-2) and bilirubin in CCl4 treated C57BL/6. Histology images indicated that the nano-cocktails at the treatment doses did not affect the organs of the mice. Importantly, the nano-cocktail reduced fibrosis of CCl4-treated mouse liver. This is the first reported data on the anti-inflammation and anti-fibrosis efficacy of Chit-IOCO in C57BL/6 mouse liver inflammation model. Overall, Chit-IOCO nanoparticles have shown great potential in MR imaging/detecting and treating/therapeutic capabilities for inflammatory diseases.

Influence of nanoparticles on the haemostatic balance: between thrombosis and haemorrhage.

Maintenance of a delicate haemostatic balance or a balance between clotting and bleeding is critical to human health. Irrespective of administration route, nanoparticles can reach the bloodstream and might interrupt the haemostatic balance by interfering with one or more components of the coagulation, anticoagulation, and fibrinolytic systems, which potentially lead to thrombosis or haemorrhage. However, inadequate understanding of their effects on the haemostatic balance, along with the fact that most studies mainly focus on the functionality of nanoparticles while forgetting or leaving behind their risk to the body's haemostatic balance, is a major concern. Hence, our review aims to provide a comprehensive depiction of nanoparticle-haemostatic balance interactions, which has not yet been covered. The synergistic roles of cells and plasma factors participating in haemostatic balance are presented. Possible interactions and interference of each type of nanoparticle with the haemostatic balance are comprehensively discussed, particularly focusing on the underlying mechanisms. Interactions of nanoparticles with innate immunity potentially linked to haemostasis are mentioned. Various physicochemical characteristics that influence the nanoparticle-haemostatic balance are detailed. Challenges and future directions are also proposed. This insight would be valuable for the establishment of nanoparticles that can either avoid unintended interference with the haemostatic balance or purposely downregulate/upregulate its key components in a controlled manner.

Poly(aspartic acid) in Biomedical Applications: From Polymerization, Modification, Properties, Degradation, and Biocompatibility to Applications.

Poly(aspartic acid) (PASP) is an anionic polypeptide that is a highly versatile, biocompatible, and biodegradable polymer that fulfils key requirements for use in a wide variety of biomedical applications. The derivatives of PASP can be readily tailored via the amine-reactive precursor, poly(succinimide) (PSI), which opens up a large window of opportunity for the design and development of novel biomaterials. PASP also has a strong affinity with calcium ions, resulting in complexation, which has been exploited for bone targeting and biomineralization. In addition, recent studies have further verified the biocompatibility and biodegradability of PASP-based polymers, which is attributed to their protein-like structure. In light of growing interest in PASP and its derivatives, this paper presents a comprehensive review on their synthesis, characterization, modification, biodegradation, biocompatibility, and applications in biomedical areas.

Different Approaches to Develop Nanosensors for Diagnosis of Diseases.

The success of clinical treatments is highly dependent on early detection and much research has been conducted to develop fast, efficient, and precise methods for this reason. Conventional methods relying on nonspecific and targeting probes are being outpaced by so-called nanosensors. Over the last two decades a variety of activatable sensors have been engineered, with a great diversity concerning the operating principle. Therefore, this review delineates the achievements made in the development of nanosensors designed for diagnosis of diseases.