Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte membranes, including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. The structure, size and surface zeta potential, and protein contents of the erythrocyte membrane-coated nanoparticles were verified using transmission electron microscopy, dynamic light scattering, and gel electrophoresis, respectively. Mice injections with fluorophore-loaded nanoparticles revealed superior circulation half-life by the erythrocyte-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. Biodistribution study revealed significant particle retention in the blood 72 h following the particle injection. The translocation of natural cellular membranes, their associated proteins, and the corresponding functionalities to the surface of synthetic particles represents a unique approach in nanoparticle functionalization.

https://www.pnas.org/content/pnas/108/27/10980.full.pdf

Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform

https://www.botanik.kit.edu/botzell/downloads/intern_Bubb_1994.pdf

Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin

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.

The rates of mechanochemical processes, such as endocytosis, membrane extension and membrane resealing after cell wounding, are known to be controlled biochemically, through interaction with regulatory proteins. Here, I propose that these rates are also controlled physically, through an apparently continuous adhesion between plasma membrane lipids and cytoskeletal proteins.

Cell control by membrane-cytoskeleton adhesion.

https://faculty.washington.edu/nsniadec/ME599/S09/private/11Dai.pdf

Membrane Tether Formation from Blebbing Cells

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.

By cosedimentation, spectrofluorimetry, and electron microscopy, we have established that actin is induced to polymerize at low salt concentrations by positively charged liposomes. This polymerization occurs only at the surface of the liposomes, and thus monomers not in direct contact with the liposome remain monomeric. The integrity of the liposome membrane is necessary to maintain actin in its polymerized state since disruption of the liposome depolymerizes actin. Actin polymerized at the surface of the liposome is organized into two filamentous structures: sheets of parallel filaments in register and a netlike organization. Spectrofluorimetric analysis with the probe N-pyrenyl-iodoacetamide shows that actin is in the F conformation, at least in the environment of the probe. However, actin assembly induced by the liposome is not accompanied by full ATP hydrolysis as observed in vitro upon addition of salts.

/pdf/polymerization-of-actin-by-positively-charged-liposomes-168955rkma.pdf

Polymerization of actin by positively charged liposomes.

Recently, we have developed a promising new drug carrier named nanoerythrosome (nEryt). This transporter are small vesicles made with the red blood cell membrane. Anticancer drugs like daunorubicin, linked to these nEryt, have a higher antineoplastic activity than the free drug. In this paper, we first analyzed the biodistribution of 125I-nEryt purified by dialysis following intravenous (i.v.) or intraperitoneal (i.p.) injections in CD1 mice. After i.v. administration, nEryt, are rapidly removed from blood circulation (< 30 min). Mainly the liver and spleen take up the vesicles. I.p. injections of nEryt purified by dialysis, showed a marked activity in the inguinal lymph nodes 2 hours post-injection. nEryt purified by centrifugation have a different biodistribution. They accumulate also in the lungs. We demonstrated that accumulation in the lungs is due to particle aggregation during the preparation procedure. Comparative analysis of size distribution of each nEryt preparation revealed that nEtyt purified by centrifugation has a mean diameter of 1.5 microm which is 10 times higher than its dialyzed counterpart. Light microscopic autoradiographs of dialyzed nEryt, reinjected i.v., showed accumulation of nEryt in the sinusoidal lumen as well as in the parenchymal cells of the liver. Autoradiographs of the spleen revealed that nEryt are distributed specifically near the marginal zone and that some of them have escaped the meshes of the red pulp cords.

Nanoerythrosomes, a new derivative of erythrocyte ghost: IV. Fate of reinjected nanoerythrosomes.

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.

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

We have investigated in the present study the interaction between G-actin and various types of liposomes, zwitterionic, positively charged, and negatively charged. To investigate at the molecular level the conformation of actin in the presence of lipids, we have selectively attached a fluorinated probe, 3-bromo-1,1,1-trifluoropropanone, to the actin cysteine residues 10, 285, and 374 and used high-resolution 19F nuclear magnetic resonance spectroscopy to investigate the probe resonances. The results indicate a change in the mobility of the 19F labels when G-actin is in the presence of positively charged liposomes made of DMPC and stearylamine and in the presence of DMPG, a negatively charged lipid. No conformational change was observed in the actin molecule in the presence of neutral liposomes. Electron micrographs of these systems reveal the formation of paracrystalline arrays of actin filaments at the surface of the positively charged liposomes, while no evidence of actin polymerization or paracrystalli...

Claude Gicquaud

Papers

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

Polymerization of actin by positively charged liposomes.

Nanoerythrosomes, a new derivative of erythrocyte ghost: IV. Fate of reinjected nanoerythrosomes.

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

Interaction between G-actin and various types of liposomes: A 19F, 31P, and 2H nuclear magnetic resonance study.