Synthesis of Nanoparticles Fully Made of Hemoglobin with Antioxidant Properties: A Step toward the Creation of Successful Oxygen Carriers

Chen, Jiantao; Jansman, Michelle Maria Theresia; Liu, Xiaoli; Hosta‐Rigau, Leticia

doi:10.1021/acs.langmuir.1c01855

Cited by 15 publications

(25 citation statements)

References 51 publications

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“…For this, the Palmer group employed glutaraldehyde and oxidized dextran to stabilize the NPs through protein cross-linking, while in our group we coated the resulting Hb-NPs with PDA through self-polymerization of dopamine. 24,36 While covalent modification of Hb with crosslinkers will inevitably alter Hb conformation that will, in turn, affect its ability to bind and release oxygen, PDA coatings also come with important limitations. These include an uncontrollable degradation behavior in physiological conditions or potential neurotoxicity issues.…”

Section: Resultsmentioning

confidence: 99%

“…Hb-NPs were first formed by desolvation precipitation following our previously reported protocol. 24 After addition of EtOH, which was used as the antisolvent to create Hb-NPs, the MPN coating was deposited by simply adding TA and a Fe 3+ solution to the suspension. The color of the suspension immediately turned dark red, indicating that the MPN coating to render MPN@Hb-NPs had been formed instantaneously (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…•− scavenging properties for trolox, MPN@Hb-NPs, and for free Hb that oxidizes into metHb in the presence of ROS. 24 However, upon increasing the concentration, the results were different and both MPN@ Hb-NPs and trolox promoted a more pronounced decrease in nAbs than free Hb. These results were more evident for the highest studied concentration (i.e., 1 mg mL −1 ) where MPN@ Hb-NPs and trolox promoted a ∼77 and ∼100% decrease in nAbs, respectively (as compared to only a ∼55% decrease for free Hb).…”

Section: Scavenging Properties Toward Reactivementioning

confidence: 99%

“…First, Hb-NPs were fabricated following our previous protocol. 24 In brief, EtOH absolute (3 mL, 4 °C) was added dropwise to a Hb solution in MQ (2 mL, 15.0 mg mL −1 , 4 °C), placed in an ice bath and under continuous stirring at 420 rpm using a magnetic stirring apparatus. The resulting turbid suspension (980 μL) was transferred to a 1.5 mL Eppendorf tube and a TA solution (10 μL, 40 mg mL −1 in MQ) was rapidly added and vortexed for 5 s. Next, FeCl 3 •6H 2 O (10 μL, 2.5 mg mL −1 in MQ) was rapidly added and the turbid suspension was vortexed by an additional 5 s. The resulting dark red turbid suspension was spun down (3000g, 5 min, 4 °C) and washed in MQ (3×, 3000g, 5 min, 4 °C) using a bench-top centrifuge (Eppendorf, centrifuge 5804R, Hamburg, Germany).…”

Section: Fabrication and Characterization Of Mpn-coatedmentioning

confidence: 99%

“…18,22,23 We recently reported a promising approach to create antioxidant HBOCs with a high Hb content by the fabrication of small solid nanoparticles (NPs) fully made of Hb (Hb-NPs). 24 We employed the desolvation precipitation method and screened several process parameters (i.e., the Hb concentration, ethanol (EtOH) to water phase ratio, sonication time, and amplitude) to obtain Hb-NPs with a size of ∼570 nm and a PDI of 0.2. Additionally, to stabilize the as-prepared Hb-NPs, a polydopamine (PDA) coating was deposited.…”

Section: Introductionmentioning

confidence: 99%

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Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

et al. 2022

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Timely administration of donor red blood cells (RBCs) is a crucial and life-saving procedure to restore tissue oxygenation in patients suffering from acute blood loss. However, important drawbacks of using allogenic RBCs are their limited availability and portability, specific storage requirements, short shelf life, or the need for blood type matching. These limitations result in serious logistical challenges that make the transfusion of donor RBCs difficult in extreme life-threatening situations prior to hospital admission. Thus, the engineering of hemoglobin (Hb) nanoparticles (Hb-NPs), which are free from the aforementioned limitations, has emerged as a promising strategy to create RBC substitutes to be used when donor blood is not available. Despite the tremendous progress achieved in recent years, many challenges still need to be overcome. For example, it is still difficult to create Hb-NPs with a high Hb content while also preventing the autoxidation of Hb into nonfunctional methemoglobin (metHb). Herein, the fabrication of small, solid Hb-NPs with an antioxidant coating is reported. By desolvation precipitation, Hb-NPs with an average hydrodynamic diameter of ∼250 nm and a polydispersity index of ∼0.2 are fabricated. A metal-phenolic network (MPN) layer consisting of a phenolic ligand (i.e., tannic acid) cross-linked through iron(III) ions is deposited onto the Hb-NPs surface to render antioxidant protection. The resulting MPN-coated Hb-NPs (MPN@Hb-NPs) maintain the ability of the encapsulated Hb to reversibly bind and release oxygen. The antioxidant properties are demonstrated, showing that MPN@Hb-NPs can effectively scavenge multiple reactive oxygen and nitrogen species, both in solution and in the presence of human RBCs and two relevant cell lines, namely, macrophages and endothelial cells. Importantly, these outstanding antioxidant properties resulting from the MPN translate into decreased metHb conversion. Finally, the newly reported MPN@Hb-NPs are also biocompatible, as shown by hemolysis rate and cell viability studies and can be used to protect the cells from oxidative damage. All in all, we have identified a novel strategy to minimize heme-mediated oxidative reactions that could potentially bring this new generation of Hb-based oxygen carriers a step closer to the clinic.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Scavenging Properties Toward Reactivementioning

confidence: 99%

Section: Fabrication and Characterization Of Mpn-coatedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

et al. 2022

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Oxygen‐Releasing Hydrogels for Tissue Regeneration

Jiang,

Zheng,

Xia

et al. 2024

Advanced NanoBiomed Research

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Hydrogels have emerged as a focal point of research in the biomedical field due to their applications in tissue repair. However, the majority of hydrogels lack the capability to release oxygen, constraining their therapeutic outcomes in environments with hypoxic tissues. In recent years, oxygen‐releasing hydrogels have garnered extensive attention in the field of tissue engineering, owing to their ability to modulate oxygen release and meet the diverse oxygenation requirements of various tissues. These hydrogels can enhance repair efficiency and promote tissue regeneration in hypoxic tissue environments. The design of oxygen‐releasing hydrogels primarily involves the utilization of diverse oxygen sources, such as algae, perfluorocarbons, and peroxides, to achieve optimal tissue oxygenation. This review provides a comprehensive summary of the design and fabrication strategies of oxygen‐releasing hydrogels, discusses deeply into their underlying oxygen‐releasing mechanisms, and their myriad applications in tissue repair along with the prospective challenges.

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Optimization and Investigation of Hemoglobin‐Loaded ZIF‐90 Metal–Organic Framework Nanoparticles as Artificial Oxygen Carriers

Douka,

Jin,

Cantallops‐Iglesias

et al. 2024

Part & Part Syst Charact

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Blood transfusions are vital, yet limited shelf‐life and storage conditions of red blood cells (RBCs) hinder their use in emergencies. Hemoglobin‐based oxygen carriers (HBOCs) aim to address these challenges, but previous versions faced clinical setbacks due to safety concerns related to hemoglobin (Hb) extravasation. ZIF‐90, a novel metal–organic framework variant where imidazole‐2‐carboxaldehyde (2‐ICA) is bridged to Zn2+ ions, is explored. Optimizing Zn2+:2‐ICA ratios and Hb concentrations, Hb‐loaded ZIF‐90 nanoparticles (NPs) are synthesized in one‐step and under mild synthesis conditions. These NPs achieve a 25.1% yield, 7.0 mg mL−1 Hb concentration, 70.3% encapsulation efficiency (EE), and 96.4% drug loading. They exhibit a left‐shifted oxygen dissociation curve with p50 of ≈8 mmHg, indicating enhanced oxygen release at lower partial oxygen pressures as compared to native RBCs. This feature makes Hb‐loaded ZIF‐90 NPs suitable for certain medical applications including ischemia‐reperfusion injury management. Furthermore, the impact of two prominent capping agents: polyvinylpyrrolidone and polyethylene glycol (PEG) is assessed. PEG improves 2‐ICA incorporation and stabilizes the ZIF‐90 crystalline phase, albeit with reduced yield, Hb content, and EE. The findings underscore the potential of Hb‐loaded ZIF‐90 NPs as next‐generation HBOCs, offering enhanced uniformity, high Hb content, and efficient oxygen binding and release properties for medical applications.

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Synthesis of Nanoparticles Fully Made of Hemoglobin with Antioxidant Properties: A Step toward the Creation of Successful Oxygen Carriers

Cited by 15 publications

References 51 publications

Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

Oxygen‐Releasing Hydrogels for Tissue Regeneration

Optimization and Investigation of Hemoglobin‐Loaded ZIF‐90 Metal–Organic Framework Nanoparticles as Artificial Oxygen Carriers

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