Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.

Integral membrane protein structure determination traditionally requires extraction from cell membranes using detergents or polymers. Here, we describe the isolation and structure determination of proteins in membrane vesicles derived directly from cells. Structures of the ion channel Slo1 from total cell membranes and from cell plasma membranes were determined at 3.8 Å and 2.7 Å resolution, respectively. The plasma membrane environment stabilizes Slo1, revealing an alteration of global helical packing, polar lipid, and cholesterol interactions that stabilize previously unresolved regions of the channel and an additional ion binding site in the Ca2+ regulatory domain. The two methods presented enable structural analysis of both internal and plasma membrane proteins without disrupting weakly interacting proteins, lipids, and cofactors that are essential to biological function.

The development of tumor acidic microenvironment-responsive theranostic agents is a research hotspot. Herein, we developed highly photostable amphiphilic croconium dye-anchored red blood cell membrane vesicle (denoted as LET-5) for tumor pH-responsive near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging-guided photothermal therapy. In tumor acidic microenvironment, both NIRF and PA signals of LET-5 were significantly enhanced and the photothermal effect of LET-5 was activated. Notably, cell membrane-based vesicle with enhanced stability and long blood circulation significantly improved the tumor accumulation of croconium dye, thus achieving better therapeutic effect than free croconium dye. These findings provide a promising approach to construct amphiphilic dye-anchored cell membrane vesicle for cancer theranostics.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

Biomedical devices trigger immune responses when implanted in the body, as they are treated as foreign bodies. To avoid inflammatory responses and enhance the biocompatibility of biomedical devices, advanced coating technology that can modulate immune responses is essential. As a part of the immune response in the body, autologous cells evade attack from macrophages using CD47 ligands that function as markers for self. Inspired by this self-recognition system, we developed a camouflage coating for biomaterial surfaces using cell membrane vesicles that could suppress inflammatory responses. In this study, we used monocyte-derived cell membrane vesicles expressing CD47 for coating nanocellulose-coated substrates. Our data showed that presentation of CD47 to macrophages elicited negative signal transduction for immunosuppression. Further, for coating, we used cell membrane vesicles and plant-derived nanofibers. We observed that the supporting layer of cellulose nanofibers physically fixed cell membrane vesicles and provided hydrophilic surfaces to the polystyrene substrate. Based on CD47 signaling, cell membrane vesicle coating suppressed the inflammatory responses of stimulated macrophages. Camouflaging biomaterial surfaces with cell-derived components might serve as an advanced coating platform to suppress inflammatory responses and enhance tissue integrity for biomedical devices after implantation.