Detoxification treatments such as toxin-targeted anti-virulence therapy offer ways to cleanse the body of virulence factors that are caused by bacterial infections, venomous injuries and biological weaponry. Because existing detoxification platforms such as antisera, monoclonal antibodies, small-molecule inhibitors and molecularly imprinted polymers act by targeting the molecular structures of toxins, customized treatments are required for different diseases. Here, we show a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists of a polymeric nanoparticle core surrounded by red blood cell membranes, absorbs membrane-damaging toxins and diverts them away from their cellular targets. In a mouse model, the nanosponges markedly reduce the toxicity of staphylococcal alpha-haemolysin (α-toxin) and thus improve the survival rate of toxin-challenged mice. This biologically inspired toxin nanosponge presents a detoxification treatment that can potentially treat a variety of injuries and diseases caused by pore-forming toxins.

A biomimetic nanosponge that absorbs pore-forming toxins.

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 RBC-encapsulated drugs are now being 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 the 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 activato...

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

Cell membrane-derived nanomaterials for biomedical applications

Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application.

Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems.

Liposomes and monoclonal antibodies are used as drug carriers for the optimal delivery of pharmacologic agents. However, they present disadvantages that led us to develop a new model of drug carriers: the nanoerythrosomes. Nanoerythrosomes are vesicles prepared by the extrusion of red blood cell ghosts, the average diameter of these vesicles is 0.1 micron. Daunorubicin was covalently linked to nanoerythrosomes and the cytotoxicity of daunorubicin conjugated to nanoerythrosomes was assessed on P388D1 cell line. The results indicated that the cytotoxicity of conjugated daunorubicin was as high as the free daunorubicin. Daunorubicin--nanoerythrosome conjugates had a higher antineoplastic activity than the free drug on CDF1 leukemia tumors. These results indicate that nonoerythrosomes could be potentially used as drug carriers.

Nanoerythrosome, a new derivative of erythrocyte ghost: preparation and antineoplastic potential as drug carrier for daunorubicin.

We have recently developed a new drug which is a carrier from red blood cell membrane. This carrier, named nanoerythrosome (nEryt), is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) was covalently conjugated to the nEryt (nEryt-DNR) using glutaraldehyde as homobifunctional linking arm. This led to a complex that is more active than free DNR both in vitro and in vivo. In this study, we identified the mechanisms that make the complex nEryt-DNR more active than free DNR. Using fluorescence microscopy and cellular-uptake, we observed that the nEryt-DNR complex cannot diffuse through the cell membrane and do not enter the cell by endocytosis. Our results suggest that the nEryt-DNR is rapidly absorbed onto the cell membrane. Free DNR is then slowly released by hydrolysis of the glutaraldehyde linking arm, producing a high concentration of free DNR in the cell's vicinity over a long period of time.

M. Moorjani

Papers

Nanoerythrosome, a new derivative of erythrocyte ghost: preparation and antineoplastic potential as drug carrier for daunorubicin.

Nanoerythrosomes, a new derivative of erythrocyte ghost II: identification of the mechanism of action.