Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited ...therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.
Due to the inherent resistance of bacterial biofilms to antibiotics and their serious threat to global public health, novel therapeutic agents and strategies to tackle biofilms are urgently needed. ...To this end, we designed and synthesized a novel guanidinium‐functionalized pillar5arene (GP5) that exhibited high antibacterial potency against Gram‐negative E. coli (BH101) and Gram‐positive S. aureus (ATCC25904) strains. More importantly, GP5 effectively disrupted preformed E. coli biofilms by efficient penetration through biofilm barriers and subsequent destruction of biofilm‐enclosed bacteria. Furthermore, host–guest complexation between GP5 and cefazolin sodium, a conventional antibiotic that otherwise shows negligible activity against biofilms, exhibited much enhanced, synergistic disruption activity against E. coli biofilms, thus providing a novel supramolecular platform to effectively disrupt biofilms.
Guanidinium‐functionalized pillar5arene (GP5) exhibited antibacterial activity against both Gram‐negative E. coli and Gram‐positive S. aureus bacterial strains. More significantly, it showed strong biofilm‐disrupting activity against preformed E. coli biofilms. Host–guest complexation between GP5 and a conventional antibiotic, cefazolin sodium, provides a supramolecular strategy for synergistically enhanced disruption of bacterial biofilms (see picture).
Paraquat, as one of the most widely used herbicides globally, is highly toxic to humans, and chronic exposure and acute ingestion leads to high morbidity and mortality rates. Here, we report ...user-friendly, photo-responsive paraquat-loaded supramolecular vesicles, prepared via one-pot self-assembly of amphiphilic, ternary host-guest complexes between cucurbit8uril, paraquat, and an azobenzene derivative. In this vesicle formulation, paraquat is only released upon UV or sunlight irradiation that converts the azobenzene derivative from its trans- to its cis- form, which in turn dissociates the ternary host-guest complexations and the vesicles. The cytotoxicity evaluation of this vesicle formulation of paraquat on in vitro cell models, in vivo zebrafish models, and mouse models demonstrates an enhanced safety profile. Additionally, the PQ-loaded vesicles' herbicidal activity against a model of invasive weed is nearly identical to that of free paraquat under natural sunlight. This study provides a safe yet effective herbicide formulation.
•Amphiphilic calix4arene (AmC4A) is synthesized to bind toxic bile acids (BAs) in a high affinity.•Establishment of a therapeutic platform based upon co-assembly of macrophage membrane and ...AmC4A.•Ursodeoxycholic acid (UDCA) was encapsulated in AmC4A for precision drug delivery into the inflammatory liver.•Targeted therapy driven by the inflammatory homing effects of macrophage membrane.•Therapy of cholestasis via the specific action of UDCA and efficient sequestration of toxic BAs and inflammatory cytokines.
Cholestasis is defined as an impairment of bile acid flow leading to intrahepatic retention of toxic bile acids (BAs), which induce apoptosis or necrosis of hepatocytes and liver inflammation. Ursodeoxycholic acid (UDCA), a FDA-approved drug to treat cholestasis, has limited therapeutic effects due to its poor specificity. Herein, we report a targeted therapeutic platform (namely, MAP) based upon co-assembly of macrophage membrane and amphiphilic calix4arene on PLGA nanoparticles. With UDCA loaded into calix4arene on the surface, MAP exhibited long-term stability, excellent biocompatibility, prolonged retention in the inflammatory liver due to the homing effects of macrophage membrane, and effective therapy of cholestasis via the specific action of UDCA and efficient sequestration of toxic BAs and inflammatory cytokines by the artificial receptor and membrane receptors, respectively. This study not only provides an artificial receptor coupled macrophage-mimetic nanomedicine platform to conquer cholestasis but also offers new insights into the design of improved versions of biomimetic nanomaterials that harness the power of both the natural and artificial receptors.
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we designed and synthesized an amphiphilic calix4arene (AmC4A) that has an outstanding capability to bind toxic BAs in a high affinity, and further coupled this artificial receptor with macrophage-membrane receptors via co-assembly on nanoparticles (namely, MAP) for the first time to targeted treatment of cholestasis in mice. As a result, MAP exhibited long-term stability and prolonged retention in the inflammatory liver, attributed to inflammatory homing effect of macrophage membrane. More importantly, MAP exhibited synergistic therapies against cholestasis via the specific delivery and associated action of UDCA and efficient sequestration of toxic BAs and inflammatory cytokines by the artificial receptor and macrophage membrane receptors, respectively.
Hydrogen energy, a new type of clean and efficient energy, has assumed precedence in decarbonizing and building a sustainable carbon-neutral economy. Recently, hydrogen production from water ...splitting has seen considerable advancements owing to its advantages such as zero carbon emissions, safety, and high product purity. To overcome the large energy barrier and high cost of water splitting, numerous efficient electrocatalysts have been designed and reported. However, various difficulties in promoting the industrialization of electrocatalytic water splitting remain. Further, as high-performance electrocatalysts that satisfy industrial requirements are urgently needed, a better understanding of water-splitting systems is required. In this paper, the latest progress in water electrolysis is reviewed, and experimental evidence from
in situ
/
operando
spectroscopic surveys and computational analyses is summarized to present a mechanistic understanding of hydrogen and oxygen evolution reactions. Furthermore, some promising strategies, including alloying, morphological engineering, interface construction, defect engineering, and strain engineering for designing and synthesizing electrocatalysts are highlighted. We believe that this review will provide a knowledge-guided design in fundamental science and further inspire technical engineering developments for constructing efficient electrocatalysts for water splitting.
Mitochondrial fission is often associated with the development of oxidative stress related diseases, as the fragmentation of mitochondria undermines their membranes, advances production of reactive ...oxygen species, and promotes apoptosis. Therefore, induction of mitochondrial aggregation and fusion could potentially reverse such medical conditions. Herein, a supramolecular strategy to induce mitochondrial aggregation and fusion is developed for the first time. A polyethylene glycol (PEG) system that was dually tagged with triphenylphosphonium (TPP) and adamantane (ADA), namely TPP-PEG-ADA, was designed to target mitochondria and functionalize their surfaces with ADA. Thereafter, the addition of cucurbit7uril (CB7) grafted hyaluronic acid (HA) induced supramolecular aggregation and fusion of mitochondria, via strong host-guest interactions between the CB7 moiety of CB7-HA and ADA residing on the surface of mitochondria. As a proof-of-principle, chemically stressed SH-SY5Y cells and zebrafish neurons were effectively protected via this supramolecular mitochondrial fusion strategy
and
, respectively. This study may open up new venues in not only fundamentally controlling mitochondrial dynamics but also addressing the medical needs to treat diseases associated with mitochondrial fission and fragmentation.
•Guanidinium-pillar5arene (GP5) may bind proteins to form nanocomplexes.•GP5 facilitates binding of proteins and cellular surface.•GP5 efficiently delivers proteins of different isoelectric points ...intracellularly.•The bioactivity of intracellularly delivered proteins are well maintained.
Guanidinium perfunctionalized pillar5arene (GP5) showed excellent potency of binding and delivering proteins of different isoelectric points and sizes into cells, and the bioactivities of the proteins were well maintained after intracellular delivery. The densely pre-organized guanidinium groups on the pillar5arene skeleton not only facilitate GP5 to bind proteins via multiple salt bridges, but also promote cellular uptake of GP5 @protein complexes. Display omitted
Due to membrane impermeability of proteins, intracellular delivery of protein is of significant challenge. Although numerous protein carriers have been reported, it remains difficult to efficiently deliver proteins with different isoelectric points into cells. Herein, guanidinium perfunctionalized pillar5arene (GP5) was employed for efficient delivery of proteins with different isoelectric points into different cell lines, and the bioactivities of the proteins were well maintained after intracellular delivery. After comparison with linear cell-penetrating peptides, unsymmetrical guanidinium-macrocycles, primary and quaternary ammonium functionalized pillar5arene derivatives, and the monomer of GP5, the high protein delivery potency of GP5 was mainly attributed to the densely pre-organized guanidinium groups on both sides of the pillar5arene skeleton, which could not only facilitate GP5 to bind with proteins to form protein nano-aggregates, but also promote cellular uptake of proteins via interactions with cellular surface. This study offers important new insights to the design and development of cell-penetrating peptide mimetic molecules for protein transductions.
In this investigation, synthesis of a surface-functionalized chitosan known as amino-rich chitosan (ARCH) was achieved by successful modification of chitosan by polyethyleneimine (PEI). The ...synthesized ARCH was characterized by a specific surface area of 8.35 m2 g−1 and a microporous structure, with pore sizes predominantly under 25 nm. The Zeta potential of ARCH maintained a strong positive charge across a wide pH range of 3–11. These characteristics contribute to its high adsorption efficiency in aqueous solutions, demonstrated by its application in removing various anionic dyes, including erioglaucine disodium salt (EDS), methyl orange (MO), amaranth (ART), tartrazine (TTZ), and hexavalent chromium ions (Cr(VI)). The adsorption capacities (Qe) for these contaminants were measured at 1301.15 mg g−1 for EDS, 1025.45 mg g−1 for MO, 940.72 mg g−1 for ART, 732.96 mg g−1 for TTZ, and 350.15 mg g−1 for Cr(VI). A significant observation was the rapid attainment of adsorption equilibrium, occurring within 10 min for ARCH. The adsorption behavior was well-described by the Pseudo-second-order and Langmuir models. Thermodynamic studies indicated that the adsorption process is spontaneous and endothermic in nature. Additionally, an increase in temperature was found to enhance the adsorption capacity of ARCH. The material demonstrated robust stability and selective adsorption capabilities in varied conditions, including different organic compounds, pH environments, sodium salt presence, and in the face of interfering ions. After five cycles of adsorption, ARCH maintained about 60% of its initial adsorption capacity. Due to its efficient adsorption performance, simple synthesis process, low biological toxicity, and cost-effectiveness, ARCH is a promising candidate for future water treatment technologies.
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•A novel surface-functionalized chitosan levelled as amino functional amino chitosan (ARCH) was synthesized by successful modification of chitosan with polyethyleneimine which resulted in improved adsorption capacity.•ARCH reached adsorption equilibrium within 10 min and the adsorption mechanism agreed with the Pseudo-second-order and Langmuir models.•Copper-loaded ARCH demonstrated robust stability and selectivity in diverse environments, including those with different pH values, various organic compounds, sodium salts, and interfering ions.•ARCH retained significant adsorption capacity of 60% even after five cycles of adsorption.•Given its numerous advantages, ARCH presents an innovative option for future water treatment technologies.•ARCH exhibits selective adsorption towards dyes.
Acute pneumonia is an inflammatory syndrome often associated with severe multi-organ dysfunction and high mortality. The therapeutic efficacy of current anti-inflammatory medicines is greatly limited ...due to the short systemic circulation and poor specificity in the lungs. New drug delivery systems (DDS) are urgently needed to efficiently transport anti-inflammatory drugs to the lungs. Here, we report an inflammation-responsive supramolecular erythrocytes-hitchhiking DDS to extend systemic circulation of the nanomedicine via hitchhiking red blood cells (RBCs) and specifically “drop off” the payloads in the inflammatory lungs. β-cyclodextrin (β-CD) modified RBCs and ferrocene (Fc) modified liposomes (NP) were prepared and co-incubated to attach NP to RBCs via β-CD/Fc host-guest interactions. RBCs extended the systemic circulation of the attached NP, meanwhile, the NP may get detached from RBCs due to the high ROS level in the inflammatory lungs. In acute pneumonia mice, this strategy delivered curcumin specifically to the lungs and effectively alleviated the inflammatory syndrome.
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•Liposomes were attached to red blood cells (RBCs) via host-guest interactions.•The supramolecular conjugates specifically “drop off” the liposomes in response to the inflammatory microenvironment.•This stragety effectively alleviated lung edema, down-regulated inflammatory cytokines, and repolarized macrophage.•This precisely controlled cell-hitchhiking strategy provides a general platform for site-specific drug delivery.
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