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We report the use of fluorinated polymer zwitterions to build hybrid systems for efficient CO2 electroreduction. The unique combination of hydrophilic phosphorylcholine and hydrophobic fluorinated moieties in these polymers creates a fractal structure with mixed branched cylinders on the surface of gold nanoparticles (AuNPs). In the presence of these polymers, the CO faradaic efficiency improves by 50-80% in the range of -0.7 V to -0.9 V. The fractal structures have a domain size of â¼3 nm, showing enhanced mass transfer kinetics of CO2 approaching the catalyst surfaces without limiting ion diffusion. The phase-separated hydrophilic and hydrophobic domains offer separated channeling to water and CO2, as confirmed by attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) and molecule dynamic (MD) simulations. H2O molecules permeate extensively into the polymer layer that adsorbs on zwitterions, forming continuous chains, while CO2 molecules strongly associate with the fluorinated tails of fluorinated polyzwitterions, with oxygen facing the positively charged amine groups. Overall, this coupling of zwitterion and fluorocarbon in a polymer material creates new opportunities for defining microenvironments of metallic nanocatalysts in hybrid structures.
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Despite the development of various drug delivery technologies, there remains a significant need for vehicles that can improve targeting and biodistribution in "hard-to-penetrate" tissues. Some solid tumors, for example, are particularly challenging to penetrate due to their dense extracellular matrix (ECM). In this study, we have formulated a new family of rod-shaped delivery vehicles named Janus base nanopieces (Rod JBNps), which are more slender than conventional spherical nanoparticles, such as lipid nanoparticles (LNPs). These JBNp nanorods are formed by bundles of DNA-inspired Janus base nanotubes (JBNts) with intercalated delivery cargoes. To develop this novel family of delivery vehicles, we employed a computation-aided design (CAD) methodology that includes molecular dynamics and response surface methodology. This approach precisely and efficiently guides experimental designs. Using an ovarian cancer model, we demonstrated that JBNps markedly improve penetration into the dense ECM of solid tumors, leading to better treatment outcomes compared to FDA-approved spherical LNP delivery. This study not only successfully developed a rod-shaped delivery vehicle for improved tissue penetration but also established a CAD methodology to effectively guide material design.
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Peptide-based hydrogels have great potential for applications in tissue engineering, drug delivery, and so on. We systematically synthesize, characterize, and investigate the self-assembly behaviors of a series of polypeptide-based penta-block copolymers by varying block sequences and lengths. The copolymers contain hydrophobic blocks of poly(γ-benzyl-l-glutamate) (PBG, Bx) and two kinds of hydrophilic blocks, poly(l-lysine) (PLL, Ky) and poly(ethylene glycol) (PEG, EG34), where x and y are the number of repeating units of each block, where PBG and PLL blocks have unique functions for nerve regeneration and cell adhesion. It shows that a sufficient length of the middle hydrophilic segment capped with hydrophobic end PBG blocks is required. They first self-assemble into flower-like micelles and sequentially form transparent hydrogels (as low as 2.3 wt %) with increased polymer concentration. The hydrogels contain a microscale porous structure, a desired property for tissue engineering to facilitate the access of nutrient flow for cell growth and drug delivery systems with high efficiency of drug storage. We hypothesize that the structure of Bx-Ky-EG34-Ky-Bx agglomerates is beyond micron size (transparent), while that of Ky-Bx-EG34-Bx-Ky is on the submicron scale (opaque). We establish a working strategy to synthesize a polypeptide-based block copolymer with a wide window of sol-gel transition. The study offers insight into rational polypeptide hydrogel design with specific morphology, exploring the novel materials as potential candidates for neural tissue engineering.
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Tetranitrato de Pentaeritritol , Rubiaceae , Hidrogéis/química , Polímeros/química , Polietilenoglicóis/química , Peptídeos/química , MicelasRESUMO
We report the effect of tail-tethering on vesiculation and complete unbinding of bilayered membranes. Amphiphilic molecules of a bolalipid, resembling the tail-tethered molecular structure of archaeal lipids, with two identical zwitterionic phosphatidylcholine headgroups self-assemble into a large flat lamellar membrane, in contrast to the multilamellar vesicles (MLVs) observed in its counterpart, monopolar nontethered zwitterionic lipids. The antivesiculation is confirmed by small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cyro-TEM). With the net charge of zero and higher bending rigidity of the membrane (confirmed by neutron spin echo (NSE) spectroscopy), the current membrane theory would predict that membranes should stack with each other (aka "bind") due to dominant van der Waals attraction, while the outcome of the nonstacking ("unbinding") membrane suggests that the theory needs to include entropic contribution for the nonvesicular structures. This report pioneers an understanding of how the tail-tethering of amphiphiles affects the structure, enabling better control over the final nanoscale morphology.
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Bicamadas Lipídicas , Fosfatidilcolinas , Espalhamento a Baixo Ângulo , Difração de Raios X , Fosfatidilcolinas/química , Estrutura Molecular , Microscopia Eletrônica de Transmissão , Bicamadas Lipídicas/químicaRESUMO
We report a facile method to prepare polymer-grafted plasmonic metal nanoparticles (NPs) that exhibit pH-responsive surface-enhanced Raman scattering (SERS). The concept is based on the use of pH-responsive polymers, such as poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH), as multidentate ligands to wrap around the surface of NPs instead of forming polymer brushes. Upon changing the solvent quality, the grafted pH-responsive polymers would drive reversible aggregation of NPs, leading to a decreased interparticle distance. This creates numerous hot spots, resulting in a secondary enhancement of SERS as compared to the SERS from discrete NPs. For negatively charged PAA-grafted NPs, the SERS response at pH 2.5 showed a secondary enhancement of up to 104-fold as compared to the response for discrete NPs at pH 12. Similarly, positively charged PAH-grafted AuNPs showed an opposite response to pH. We demonstrated that enhanced SERS with thiol-containing and charged molecular probes was indeed from the pH-driven solubility change of polymer ligands. Our method is different from the conventional SERS sensors in the solid state. With pH-responsive polymer-grafted NPs, SERS can be performed in solution with high reproducibility and sensitivity but without the need for sample pre-concentration. These findings could pave the way for innovative designs of polymer ligands for metal NPs where polymer ligands do not compromise interparticle plasmon coupling.
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Stimuli-responsive microgels, composed of small beads with soft, deformable polymer networks swollen through a combination of synthetic control over the polymer and its interaction with water, form a versatile platform for development of multifunctional and biocompatible sensors. The interfacial structural variation of such materials at a nanometer length scale is essential to their function, but not yet fully comprehended. Here, we take advantage of the plasmonic response of a gold nanorod embedded in a thermoresponsive microgel (AuNR@PNIPMAm) to monitor structural changes in the hydrogel directly near the nanorod surface. By direct comparison of the plasmon response against measurements of the hydrogel structure from dynamic light scattering and nuclear magnetic resonance, we find that the microgel shell of batch-polymerized AuNR@PNIPMAm exhibits a heterogeneous volume phase transition reflected by different onset temperatures for changes in the hydrodyanmic radius (RH) and plasmon resonance, respectively. The new approach of contrasting plasmonic response (a measure of local surface hydrogel structure) with RH and relaxation times paves a new path to gain valuable insight for the design of plasmonic sensors based on stimuli-responsive hydrogels.
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Bicellar systems have become popularized as their rich morphology can be applied in biochemistry, physical chemistry, and drug delivery technology. To the biochemical field, bicelles are powerful model membranes for the study of transmembrane protein behavior, membrane transport, and environmental interactions with the cell. Their morphological responses to environmental changes reveal a profound fundamental understanding of physical chemistry related to the principle of self-assembly. Recently, they have also drawn significant attention as theranostic nanocarriers in biopharmaceutical and diagnostic research due to their superior cellular uptake compared to liposomes. It is evident that applications are becoming broader, demanding to understand how the bicelle will form and behave in various environments. To consolidate current works on the bicelle's modern applications, this review will discuss various effects of composition and environmental conditions on the morphology, phase behavior, and stability. Furthermore, various applications such as payload entrapment and polymerization templating are presented to demonstrate their versatility and chemical nature.
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We report a generalized platform for synthesizing a polymer nanoweb with a high specific surface area via a bicellar template, composed of 1,2-dipalmitoyl phosphocholine (DPPC), 1,2-dihexanoyl phosphocholine (DHPC), and 1,2-dipalmitoyl phosphoglycerol (DPPG). The pristine bicelle (in the absence of monomer or polymer) yields a variety of well-defined structures, including disc, vesicle, and perforated lamella. The addition of styrene monomers in the mixture causes bicelles to transform into lamellae. Monomers are miscible with DPPC and DPPG initially, while polymerization drives polymers to the DHPC-rich domain, resulting in a polymer nanoweb supported by the outcomes of small angle neutron scattering, differential scanning calorimetry, and transmission electron microscopy.
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Control of interparticle interactions in terms of their direction and strength highly relies on the use of anisotropic ligand grafting on nanoparticle (NP) building blocks. We report a ligand deficiency exchange strategy to achieve site-specific polymer grafting of gold nanorods (AuNRs). Patchy AuNRs with controllable surface coverage can be obtained during ligand exchange with a hydrophobic polystyrene ligand and an amphiphilic surfactant while adjusting the ligand concentration (CPS) and solvent condition (Cwater in dimethylformamide). At a low grafting density of ≤0.08 chains/nm2, dumbbell-like AuNRs with two polymer domains capped at the two ends can be synthesized through surface dewetting with a high purity of >94%. These site-specifically-modified AuNRs exhibit great colloidal stability in aqueous solution. Dumbbell-like AuNRs can further undergo supracolloidal polymerization upon thermal annealing to form one-dimensional plasmon chains of AuNRs. Such supracolloidal polymerization follows the temperature-solvent superposition principle as revealed by kinetic studies. Using the copolymerization of two AuNRs with different aspect ratios, we demonstrate the design of chain architectures by varying the reactivity of nanorod building blocks. Our results provide insights into the postsynthetic design of anisotropic NPs that potentially serve as units for polymer-guided supracolloidal self-assembly.
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Many diseases, especially cancer, are caused by the abnormal expression of non-coding microRNAs (miRNAs), which regulate gene expression, leading to the development of miRNA-based therapeutics. Synthetic miRNA inhibitors have shown promising efficacy in blocking the activity of aberrant miRNAs that are upregulated in disease-specific pathologies. On the other hand, miRNAs that aid in preventing certain diseases and are reduced in expression in the disease state need different strategies. To tackle this, miRNA mimics, which mimic the activity of endogenous miRNAs, can be delivered for those miRNAs downregulated in different disease states. However, the delivery of miRNA mimics remains a challenge. Here, we report a cationic polylactic-co-glycolic acid (PLGA)-poly-L-histidine delivery system to deliver miRNA mimics. We chose miR-34a mimics as a proof of concept for miRNA delivery. miR-34a-loaded PLGA-poly-L-histidine nanoparticles (NPs) were formulated and biophysically characterized to analyze the structural properties of miRNA mimic-loaded NPs. In vitro efficacy was determined by investigating miR-34a and downstream target levels and performing cell viability and apoptosis assays. We confirmed in vivo efficacy through prolonged survival of miR-34a NP-treated A549-derived xenograft mice treated intratumorally. The results of these studies establish PLGA-poly-L-histidine NPs as an effective delivery system for miRNA mimics for treating diseases characterized by downregulated miRNAs.
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Bicellar mixtures have been used as alignable membrane substrates under a magnetic field applicable for the structural characterization of membrane-associated proteins. Recently, it has shown that bicelles can serve as nanocarriers to effectively deliver hydrophobic therapeutic molecules to cancer cells with a three- to ten-fold enhancement compared to that of liposomes of a chemically identical composition. In this chapter, detailed preparation protocol, common structural characterization methods, the structural stability, the cellular uptake and a few unique functions of bicellar nanodiscs are discussed.
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Lipossomos , Espalhamento a Baixo ÂnguloRESUMO
Bicelles are discoidal lipid nanoparticles (LNPs) in which the planar bilayer and curved rim are, respectively, composed of long- and short-chain lipids. Bicellar LNPs have a hydrophobic core, allowing hydrophobic molecules and large molecular complexes such as quantum dots (QDs) to be encapsulated. In this study, CdSe/ZnS QDs were encapsulated in bicelles made of dipalmitoyl phosphatidylcholine, dihexanoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol, and distearoyl phosphatidylethanolamine conjugated with polyethylene glycerol amine 2000 to form a well-defined bicelle-QD nanocomplex (known as NANO2-QD or bicelle-QD). The bicelle-QD was then incubated with Hek293t cells and HeLa cells for different periods of time to determine changes in their cellular localization. Bicelle-QDs readily penetrated Hek293t cell membranes within 15 min of incubation, localized to the cytoplasm, and associated with mitochondria and intracellular vesicles. After 1 h, the bicelle-QDs enter the cell nucleus. Large aggregates form throughout the cell after 2 h and QDs are nearly absent from the nucleus by 4 h. Previous reports have demonstrated that CdSe/ZnS QDs can be toxic to cells, and we have found that encapsulating QDs in bicelles can attenuate but did not eliminate cytotoxicity. The present research outcome demonstrates the time-resolved pathway of bicelle-encapsulated QDs in Hek293t cells, morphological evolution in cells over time, and cytotoxicity of the bicelle-QDs, providing important insight into the potential application of the nanocomplex for cellular imaging.
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Nanocompostos , Pontos Quânticos , Humanos , Células HeLa , Pontos Quânticos/toxicidade , Pontos Quânticos/química , Células HEK293 , Nanocompostos/toxicidadeRESUMO
The amount of water in therapeutic nanoparticles (NPs) is of great importance to the pharmaceutical industry, as water content reflects the volume occupied by the solid components. For example, certain biomolecules, such as mRNA, can undergo conformational change or degradation when exposed to water. Using static light scattering (SLS) and dynamic light scattering (DLS), we estimated the water content of NPs, including extruded liposomes of two different sizes and polystyrene (PS) Latex NPs. In addition, we used small-angle neutron scattering (SANS) to independently access the water content of the samples. The water content of NPs estimated by SLS/DLS was systematically higher than that from SANS. The discrepancy is most likely attributed to the larger radius determined by DLS, in contrast to the SANS-derived radius observed by SANS. However, because of low accessibility to the neutron facilities, we validate the combined SLS/DLS to be a reasonable alternative to SANS for determining the water (or solvent) content of NPs.
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Nanopartículas , Água , Espalhamento a Baixo Ângulo , Difração de Nêutrons , NêutronsRESUMO
HYPOTHESIS: A well-defined discoidal bicelle composed of three lipids, specifically zwitterionic long-chain 1,2dipalmitoyl phosphocholine (DPPC) and short-chain 1,2dihexanoyl phosphocholine (DHPC) doped with anionic 1,2dipalmitoyl phosphoglycerol (DPPG) provides a generalized template for the synthesis of hydrophobic polymer nano-rings. The lipid molar ratio of DPPC/DHPC/DPPG is 0.71/0.25/0.04. The detailed investigation and discussion were based on styrene but tested on three other vinyl monomers. EXPERIMENTS: The structure of nano-rings is identified through the detailed analysis of small angle X-ray/neutron scattering (SAXS and SANS) data and transmission electron micrographs (TEM), supported by the differential scanning calorimetric (DSC) data before and after polymerization. The investigation covers samples with a styrene-to-lipid ratio ranged varied from 1:50 to 1:10. FINDINGS: The styrene monomers are initially located at both the discoidal planar (long-chain lipid rich) and rim (short-chain lipid rich) regions. During polymerization, they migrate to the more fluid rim regionsection. The formation mechanism involves the interplay of hydrophobic interaction, mismatched miscibility of polystyrene between the ordered and disordered phases, and crystallinity of the long lipid acyl chains. This facile synthesis is proven applicable for several hydrophobic monomers. The well-defined nano-rings greatly enhance the interfacial area and have the potential to be the building blocks for functional materials, if monomers are incorporated with desirable functions, for future applications.
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Fosforilcolina , Polímeros , Espalhamento a Baixo Ângulo , Polimerização , Difração de Raios X , Éteres Fosfolipídicos , Estirenos , Bicamadas Lipídicas/químicaRESUMO
Manipulating molecular and supramolecular interactions within cellulose nanocrystals (CNCs) to introduce different levels of assemblies combined with multiple functionalities is required for the development of degradable smart materials from renewable resources. To attain hierarchical structures and stimuli-responsive properties, a new class of liquid crystalline cellulosic hybrid materials is synthesized. Herein, main-chain rigid-rod-like oxidized cellulose (CNC-COOH) is prepared from a Cellulose Whatman filter paper (Cellulose W.P.) by acid hydrolysis and oxidized using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Thermotropic LC molecule, 4-cyano-4'-hydroxybiphenyl with a 12-methylene spacer (CB12-OH) is grafted onto the carboxylic acid group of CNC-COOH via Steglich esterification. The liquid crystalline functionalized CNCs cellulose nanocrystals (CNC-COO-CB12) are readily soluble in DMSO and ionic liquids. The extent of functionalization and structure of CNC-COO-CB12 are confirmed by solution-state 1H NMR and supported by other characterization techniques. We investigate the interplay of liquid crystalline orientational order of CNCs and cyanobiphenyl (CB12), and the supramolecular hydrogen bonding of CNCs within CNC-COO-CB12 and compare it with CNC-COOH. The introduction of thermotropic CB12 side chains onto rigid-rod CNCs shows the exclusive formation of smectic mesophases from the assemblies of CB12 with the absence of the cholesteric mesophase typically observed from CNC-COOH as verified by temperature-controlled SAXS (T-SAXS). This is further verified by UV-visible and SEM studies that show CNC-COO-CB12 forms smectic domains while CNC-COOH forms a visible light reflecting cholesteric mesophase in dried films. Thus, the interplay of liquid crystalline order of CNCs and CB12 and supramolecular hydrogen bonding of CNCs results in ordered, smectic-mesostructured CNCs for use in stimuli-responsive functional materials.
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Background: Combination antiretroviral therapy has significantly advanced HIV-1 infection treatment. However, HIV-1 remains persistent in the brain; the inaccessibility of the blood-brain barrier allows for persistent HIV-1 infections and neuroinflammation. Nanotechnology-based drug carriers such as nanodiscoidal bicelles can provide a solution to combat this challenge. Methods: This study investigated the safety and extended release of a combination antiretroviral therapy drug (tenofovir)-loaded nanodiscs for HIV-1 treatment in the brain both in vitro and in vivo. Result: The nanodiscs entrapped the drug in their interior hydrophobic core and released the payload at the desired location and in a controlled release pattern. The study also included a comparative pharmacokinetic analysis of nanodisc formulations in in vitro and in vivo models. Conclusion: The study provides potential applications of nanodiscs for HIV-1 therapy development.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Tenofovir , Preparações de Ação Retardada/farmacologia , Infecções por HIV/tratamento farmacológico , Portadores de Fármacos/química , Encéfalo , Lipídeos/uso terapêutico , Fármacos Anti-HIV/uso terapêuticoRESUMO
We report a new design of polymer-patched gold nanoparticles (AuNPs) with controllable interparticle interactions in terms of their direction and strength. Patchy AuNPs (pAuNPs) are prepared through hydrophobicity-driven surface dewetting under deficient ligand exchange conditions. Using the exposed surface on pAuNPs as seeds, a highly controllable growth of AuNPs is carried out via seed-mediated growth while retaining the size of polymer domains. As guided by ligands, these pAuNPs can self-assemble directionally in two ways along the exposed surface (head-to-head) or the polymer-patched surface of pAuNPs (tail-to-tail). Control of the surface asymmetry/coverage on pAuNPs provides an important tool in balancing interparticle interactions (attraction vs. repulsion) that further tunes assembled nanostructures as clusters and nanochains. The self-assembly pathway plays a key role in determining the interparticle distance and therefore plasmon coupling of pAuNPs. Our results demonstrate a new paradigm in the directional self-assembly of anisotropic building blocks for hierarchical nanomaterials with interesting optical properties.
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Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and dipalmitoyl phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis of small angle neutron scattering and small angle X-ray scattering data, the two DSC peaks are associated with the melting of DPPC and a change in bicellar morphologyânamely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility of the two structural transformations was examined by DSC and found to be consistent with the corresponding small angle scattering data. However, the peak that is not associated with the melting of DPPC does not correspond to any structural transformation for bicelles containing distearoyl phosphatidylethanolamine conjugated with polyethylene glycol. Based on complementary experimental data, we conclude that membrane flexibility, lipid miscibility, and differential solubility between the long- and short-chain lipids in water are important parameters controlling the reversibility of morphologies experienced by the bicelles.
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1,2-Dipalmitoilfosfatidilcolina , Micelas , 1,2-Dipalmitoilfosfatidilcolina/química , Varredura Diferencial de Calorimetria , Bicamadas Lipídicas/química , Polietilenoglicóis/química , Espalhamento a Baixo Ângulo , TemperaturaRESUMO
Peptide nucleic acids (PNAs) are nucleic acid analogs with superior hybridization properties and enzymatic stability than deoxyribonucleic acid (DNA). In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymer due to the Watson-Crick -based molecular recognition and flexibility of synthesis. Here, we engineered PNA amphiphiles using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γPNA) amphiphiles self-assemble into spherical vesicles. Further, we formulate nano-assemblies using the amphiphilic γPNA as a polymer via ethanol injection-based protocols. We perform comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and nano-assemblies. Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) analysis reveal ellipsoidal morphology of γPNA nano-assemblies that results in superior cellular delivery compate to the spherical self-assembly. Next, we compare the functional activities of γPNA self-and nano-assemblies in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays. Overall, we establish that γPNA amphiphile is a functionally active bio-polymer to formulate nano-assemblies for a wide range of biomedical applications.
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Outer membrane vesicles (OMVs) are nanoscale spherical vesicles released from Gram-negative bacteria. The lipid bilayer membrane structure of OMVs consists of similar components as bacterial membrane and thus has attracted more and more attention in exploiting OMVs' bio-applications. Although the endotoxic lipopolysaccharide on natural OMVs may impose potential limits on their clinical applications, genetic modification can reduce their endotoxicity and decorate OMVs with multiple functional proteins. These genetically engineered OMVs have been employed in various fields including vaccination, drug delivery, cancer therapy, bioimaging, biosensing, and enzyme carrier. This review will first briefly introduce the background of OMVs followed by recent advances in functionalization and various applications of engineered OMVs with an emphasis on the working principles and their performance, and then discuss about the future trends of OMVs in biomedical applications.