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Doxorubicin (DOX) is an effective chemotherapeutic agent widely used for cancer treatment. However, hypoxia in tumour tissue and obvious adverse effects particularly cardiotoxicity restricts the clinical usage of DOX. Our study is based on the co-administration of haemoglobin-based oxygen carriers (HBOCs) and DOX in a breast cancer model to investigate HBOCs' ability to enhance chemotherapeutic effectiveness and its capabilities to alleviate the side effects induced by DOX. In an in-vitro study, the results suggested the cytotoxicity of DOX was significantly improved when combined with HBOCs in a hypoxic environment, and produced more γ-H2AX indicating higher DNA damage than free DOX did. Compared with administration of free DOX, combined therapy exhibited a stronger tumour suppressive effect in an in-vivo study. Further mechanism studies showed that the expression of various proteins such as hypoxia-inducible factor-1α (HIF-1α), CD31, CD34, and vascular endothelial growth factor (VEGF) in tumour tissues was also significantly reduced in the combined treatment group. In addition, HBOCs can significantly reduce the splenocardiac toxicity induced by DOX, according to the results of the haematoxylin and eosin (H&E) staining and histological investigation. This study suggested that PEG-conjugated bovine haemoglobin may not only reduce the hypoxia in tumours and increase the efficiency of chemotherapeutic agent DOX, but also alleviate the irreversible heart toxicity caused by DOX-inducted splenocardiac dysregulation.

Oxygen tension at 50% haemoglobin saturation (P 50 ), which reflects the degree of peripheral oxygen offloading and tissue oxygenation, plays an important role in the diagnosis and treatment of disease, as well as in transfusion research. Blood gas analysers are commonly used in clinical and obtain P 50 values through complex calculations and analysis. Oxygenation-dissociation analysers are specially designed to record the oxygen dissociation curves and obtain P 50 values of whole blood, red blood cells (RBCs), and stroma-free haemoglobin. However, whether the two equipment obtain comparable data is still uncertain. Herein, we used both equipment to detect P 50 values of blood and stroma-free haemoglobin from human and bovine sources, venous and arterial blood of beagle and rat, and stored rat blood. For human blood, both analysers yielded similar data. P 50 of the stroma-free haemoglobin and bovine blood could only be properly detected by oxygenation-dissociation analysers. Blood gas analysers showed different P 50 values, while oxygenation-dissociation analysers got similar P 50 values for arterial and venous samples. Oxygenation-dissociation analysers distinguished changes in P 50 values during RBCs storage. Compared with the blood gas analysers, oxygenation-dissociation analysers had a stronger detection capability in P 50 measurement with regard to both sample types and species.

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.

Oxidative toxicity has impeded the development of haemoglobin-based oxygen carriers (HBOCs) by causing methaemoglobin (MetHb) formation and inducing oxidative stress. In our previous work, polydopamine-coated haemoglobin (Hb-PDA) nanoparticles have been designed and synthesized with the capacity to reduce oxidative toxicity. In this investigation, the mass ratio of dopamine (DA) to haemoglobin (Hb) and the pH value are found to be the primary factors that influence preparation of Hb-PDA nanoparticles. X-ray photoelectron spectroscopy showed that the catechol groups of DA play a crucial role in the modification of Hb surface. Hb-PDA nanoparticles were found to exhibit oxidative protection from hydrogen peroxide (H 2 O 2 ) and the change of mitochondrial membrane potential showed that the Hb-PDA nanoparticles reduced H 2 O 2 -induced apoptosis. It is demonstrated that modification of PDA could maintain the oxygen-release capacity of Hb. These findings confirm that Hb-PDA nanoparticles possess restrained oxidative toxicity and preserve oxygen-release capacity.

Methemoglobin concentration is an important pathophysiological biomarker, reflecting the oxygen-carrying and oxygen-releasing capabilities of hemoglobin (Hb). Raman spectroscopy is used to develop a novel technique for determining the methemoglobin concentration. Raman activity combined with two-dimensional correlation analysis is an attractive method for investigating Hb oxidation, exhibiting several relevant peaks in the range of 1200-1650 cm(-1). Methemoglobin concentration is estimated by measuring the intensity of Raman peaks in the ranges of 1210-1230 cm(-1) and 1340-1380 cm(-1) with 785-nm excitation. The correlation between Raman-based methemoglobin concentration estimations and the methemoglobin concentration measured using spectrophotometry was highly significant. These results suggest the potential of Raman spectroscopy as a new quantitative approach to determine the methemoglobin concentration.