Red blood cell phagocytosis following hexokinase inactivation

Chiarantini, Laura; Antonelli, A.; Rossi, Luigia; Fraternale, Alessandra; Magnani, Mauro

doi:10.1002/cbf.290120310

Cited by 7 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HK and G6PDH catalyze the first steps of NADPH supply, thus Schuster et al (1989) and Schuster and Holzhutter (1995) showed by mathematical simulations that the threshold of tolerance for energy and oxidative loads are reduced in cases of deficiency of these two enzymes. And it has been reported that decreased HK (Chiarantini et al, 1994) and G6PDH activities (Ciftci et al, 2002) result in more rapid loss of RBC integrity on addition of oxidizing agents. Our results were consistent with these findings: Fig.…”

Section: Failure Of Homeostasismentioning

confidence: 97%

“…Does metabolic collapse signal RBC removal during their normal senescence, and in the erythroenzymopathies that cause haemolytic anaemia? A number of hypotheses based on previous in silico analyses (Schuster and Holzhutter, 1995;Martinov et al, 2000;Ç akir et al, 2004) and on experimental observations (Beutler, 1988;Piomelli and Seaman, 1991;Magnani et al, 1991;Samaja et al, 1991;Chiarantini et al, 1994;Fiorani et al, 2000Fiorani et al, , 1997 have been proposed. In the present work, we performed in silico simulations using the model of human RBC metabolism that was based on NMR data and developed by Mulquiney and Kuchel (1999); it was used to explore metabolic collapse, and the crucial events that precede this collapse when enzyme activities decline.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Metabolic homeostasis in the human erythrocyte: In silico analysis

et al. 2006

View full text Add to dashboard Cite

Section: Failure Of Homeostasismentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Metabolic homeostasis in the human erythrocyte: In silico analysis

et al. 2006

View full text Add to dashboard Cite

“…For example, anti-viral drug azidothymidine (AZT) was loaded in carrier RBC83 that delivered cargo to macrophages and provided enhanced anti-viral potency vs free drug in cell culture26,84 and in a mouse model of HIV infection85. Encouraging results have been obtained in cells with RBC-mediated delivery of other anti-viral agents86–90 including antisense agents inhibiting HIV-1 replication in infected cells91. These studies provide a basis for a wide-range antiviral strategy87,92,93 posed for systematic testing in animal models and human studies.…”

Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcmentioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

342

294

View full text Add to dashboard Cite

Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

show abstract

“…Another method is treatment with reagents that cause clustering of the band 3 protein, for example, by a bifunctional amine-amine cross-linking agent, bisulfosuccinimidyl suberate (BS 3 ) in ZnCl 2 medium [167,168], which leads to the binding of Hb and proteins of the membrane and fixation of complement components on the cell surface [169]. Inactivation of intracellular hexokinase is also described, which leads to disruption of the cell metabolism and a decrease in the concentration of ATP necessary for cell survival [170].…”

Section: Erythrocytes For Targeted Drug Deliverymentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

View full text Add to dashboard Cite

Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

show abstract

Red blood cell phagocytosis following hexokinase inactivation

Cited by 7 publications

References 17 publications

Metabolic homeostasis in the human erythrocyte: In silico analysis

Metabolic homeostasis in the human erythrocyte: In silico analysis

Drug delivery by red blood cells: vascular carriers designed by mother nature

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Contact Info

Product

Resources

About