Detoxification treatments such as toxin-targeted anti-virulence therapy1, 2 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 antisera3, monoclonal antibodies4, small-molecule inhibitors5, 6, and molecularly imprinted polymers7 act by targeting the molecular structures of the 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-hemolysin (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.

Synthetic nanoparticles coated with cellular membranes have been increasingly explored to harness natural cell functions toward the development of novel therapeutic strategies. Herein, we report on a unique bacterial membrane-coated nanoparticle system as a new and exciting antibacterial vaccine. Using Escherichia coli as a model pathogen, we collect bacterial outer membrane vesicles (OMVs) and successfully coat them onto small gold nanoparticles (AuNPs) with a diameter of 30 nm. The resulting bacterial membrane-coated AuNPs (BM-AuNPs) show markedly enhanced stability in biological buffer solutions. When injected subcutaneously, the BM-AuNPs induce rapid activation and maturation of dendritic cells in the lymph nodes of the vaccinated mice. In addition, vaccination with BM-AuNPs generates antibody responses that are durable and of higher avidity than those elicited by OMVs only. The BM-AuNPs also induce an elevated production of interferon gamma (INFγ) and interleukin-17 (IL-17), but not interleukin-4 (IL-4), indicating its capability of generating strong Th1 and Th17 biased cell responses against the source bacteria. These observed results demonstrate that using natural bacterial membranes to coat synthetic nanoparticles holds great promise for designing effective antibacterial vaccines.

The unique structural features and stealth properties of a recently developed red blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over the interfacial interactions between natural cellular membranes and polymeric nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are examined, including completeness of membrane coverage, membrane sidedness upon coating, and the effects of polymeric particles’ surface charge and surface curvature on the membrane cloaking process. The study shows that RBC membranes completely cover negatively charged polymeric nanoparticles in a right-side-out manner and enhance the particles’ colloidal stability. The membrane cloaking process is applicable to particle substrates with a diameter ranging from 65 to 340 nm. Additionally, the study reveals that both surface glycans on RBC membranes and the substrate properties play a significant role in driving and directing the membrane/particle assembly. These findings further the understanding of the dynamics between cellular membranes and nanoscale substrates and provide valuable information toward future development and characterization of cellular membrane-cloaked nanodevices.

Toxoid vaccines—vaccines based on inactivated bacterial toxins— are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections1–4. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal α-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. As compared to vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate the reported study to open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

Herein recent progress in developing red blood cell (RBC)-inspired delivery systems is reviewed, with an emphasis on how our growing understanding of fundamental biological properties of natural RBCs has been applied in the design and engineering of these delivery systems. Specifically, progress achieved in developing carrier RBCs, a class of delivery vehicles engineered by directly loading natural RBCs with therapeutic agents, will be reviewed. Then alternative approaches to engineering synthetic vehicles through mimicking the mechanobiological and chemico-biological properties of natural RBCs will be considered. The synthesis and application of RBC membrane-derived vesicles, of which the natural RBC membranes are collected and directly utilized to prepare drug carriers, will then be discussed. Finally, a recent approach in engineering RBC membrane-camouflaged nanoparticle systems that combine advantages of natural RBCs and synthetic biomaterials will be highlighted. These developments indicate that RBC-inspired delivery systems will result in next-generation nanomedicine with extensive medical applications.

We investigate the ‘marker-of-self’ functionalization of nanoparticles through coating of natural RBC membranes. The membrane translocation approach is shown to be highly efficient and bestows nanoparticles with correctly oriented and functional immunomodulatory proteins such as CD47 at equivalent density to natural RBCs.

Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression. Inspired by antibody-driven pathology, we used intact RBC membranes stabilized by biodegradable polymeric nanoparticle cores to serve as an alternative target for pathological antibodies in an antibody-induced anemia disease model. Through both in vitro and in vivo studies, we demonstrated efficacy of RBC membrane-cloaked nanoparticles to bind and neutralize anti-RBC polyclonal IgG effectively, and thus preserve circulating RBCs.nanomedicine | immune therapy | type II hypersensitivity reaction | autoantibody

Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare.