Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury.

Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

Liquid Crystal Electrolyte with Lamellar Ionic Channels for All-In-One Gel Flexible Supercapacitor.

Liquid crystalline hydrogels with nanoscale order are an attractive soft material to transport ions or electrons with high efficiency. By employing noncovalent interactions between amphiphiles and solvents, defined anisotropic ordered structures can assemble that serve as interior transmissible channels. Herein, the phase behaviors of a polymerizable amphiphile of 1-vinyl-3-alkylimidazolium bromide (VCn IMBr, n = 12, 14, 16) are investigated at different concentrations in a deep eutectic solvent. The aggregation such as micelle, hexagonal, and lamellar liquid crystal phase is created. Through in-phase polymerization, the lamellar structures within an an isotropic liquid crystal can be well solidified to obtain a conductive gel electrolyte. A sandwich-structured all-in-one gel flexible supercapacitor is then built with this specific gel electrolyte. With greatly increased adhesion and minimized interfacial resistance between electrode and electrolyte, the approach will be able to create energy-storage devices with anisotropic ionic and electronic charge transportations envisioned for various electrochemical applications.

Huge Electron Sponge of Polyoxometalate toward Advanced Lithium-Ion Storage.

The huge polyoxometalate, Na48[HxMo256VIMo112VO1032(H2O)240(SO4)48] ({Mo368}), which can be prepared by a facile solution process and can be applied in lithium-ion storage applications as the anode. The large and open hollow nanostructure is promising to store a larger number of lithium ions and expedite the diffusion of lithium ions. A single {Mo368} nanocluster can transfer 624 electrons, referred to as a "huge electron sponge". Pure {Mo368} without any support materials exhibits very high capacities of 964 mA h g-1 with hardly any decay for 100 cycles at 0.1 A g-1 and still maintains 761 mA h g-1 after 180 cycles at 0.5 A g-1, indicating great cycling stability. The {Mo368} anode provides excellent rate performance and reversibility during the lithiation/delithiation processes, which are contributed by both the diffusion-controlled process and the capacitive process. The capacitive contribution can reach 71.7% at a scan rate of 2 mV s-1. The high DLi+ value measured by GITT confirms the fast reaction kinetics of the {Mo368} electrode. The {Mo368}//NCM111-A full cell is practically applied to light LED lamps. These investigations indicate that {Mo368} nanoclusters are advanced energy storage materials with high capacities, fast charge transfer, and low-cost mass production for lithium-ion storage. Moreover, {Mo368} should be considered a clean energy material because there is no production of environmental pollution during the charge/discharge processes.

Using deep learning models in magnetic resonance cholangiopancreatography images to diagnose common bile duct stones.

BACKGROUNDS AND AIMS: Magnetic resonance cholangiopancreatography (MRCP) plays a significant role in diagnosing common bile duct stones (CBDS). Currently, there are no studies to detect CBDS by using the deep learning (DL) model in MRCP. This study aimed to use the DL model You Only Look Once version 5 (YOLOv5) to diagnose CBDS in MRCP images and verify its validity compared to the accuracy of radiologists. METHODS: By collecting the thick-slab MRCP images of patients diagnosed with CBDS, 4 submodels of YOLOv5 were used to train and validate the performance. Precision, recall rate, and mean average precision (mAP) were used to evaluate model performance. Analyze possible reasons that may affect detection accuracy by validating MRCP images in 63 CBDS patients and comparing them with radiologist detection accuracy. Calculate the correctness of YOLOv5 for detecting one CBDS and multiple CBDS separately. RESULTS: The precision of YOLOv5l (0.970) was higher than that of YOLOv5x (0.909), YOLOv5m (0.874), and YOLOv5s (0.939). The mAP did not differ significantly between the 4 submodels, with the following results: YOLOv5l (0.942), YOLOv5x (0.947), YOLO5s (0.927), and YOLOv5m (0.946). However, in terms of training time, YOLOv5s was the fastest (4.8 h), detecting CBDS in only 7.2 milliseconds per image. In 63 patients the YOLOv5l model detected CBDS with an accuracy of 90.5% compared to 92.1% for radiologists, analyzing the difference between the positive group successfully identified and the unidentified negative group not. The incorporated variables include common bile duct diameter > 1 cm (p = .560), combined gallbladder stones (p = .706), maximum stone diameter (p = .057), combined cholangitis (p = .846), and combined pancreatitis (p = .656), and the number of CBDS (p = .415). When only one CBDS was present, the accuracy rate reached 94%. When multiple CBDSs were present, the recognition rate dropped to 70%. CONCLUSION: YOLOv5l is the model with the best results and is almost as accurate as the radiologist's detection of CBDS and is also capable of detecting the number of CBDS. Although the accuracy of the test gradually decreases as the number of stones increases, it can still be useful for the clinician's initial diagnosis.

Metal Ion-Directed Functional Metal-Phenolic Materials.

Metal ions are ubiquitous in nature and play significant roles in assembling functional materials in fields spanning chemistry, biology, and materials science. Metal-phenolic materials are assembled from phenolic components in the presence of metal ions through the formation of metal-organic complexes. Alkali, alkali-earth, transition, and noble metal ions as well as metalloids interacting with phenolic building blocks have been widely exploited to generate diverse hybrid materials. Despite extensive studies on the synthesis of metal-phenolic materials, a comprehensive summary of how metal ions guide the assembly of phenolic compounds is lacking. A fundamental understanding of the roles of metal ions in metal-phenolic materials engineering will facilitate the assembly of materials with specific and functional properties. In this review, we focus on the diversity and function of metal ions in metal-phenolic material engineering and emerging applications. Specifically, we discuss the range of underlying interactions, including (i) cation-π, (ii) coordination, (iii) redox, and (iv) dynamic covalent interactions, and highlight the wide range of material properties resulting from these interactions. Applications (e.g., biological, catalytic, and environmental) and perspectives of metal-phenolic materials are also highlighted.

Highly Interfacial Active Gemini Surfactants as Simple and Versatile Emulsifiers for Stabilizing, Lubricating and Structuring Liquids.

To date, locking the shape of liquids into non-equilibrium states usually relies on jamming nanoparticle surfactants at an oil/water interface. Here we show that a synthetic water-soluble zwitterionic Gemini surfactant can serve as an alternative to nanoparticle surfactants for stabilizing, structuring and additionally lubricating liquids. By having a high binding energy comparable to amphiphilic nanoparticles at the paraffin oil/water interface, the surfactant can attain near-zero interfacial tensions and ultrahigh surface coverages after spontaneous adsorption. Owing to the strong association between neighboring surfactant molecules, closely packed monolayers with high mechanical elasticity can be generated at the oil/water interface, thus allowing the surfactant to produce not only ultra-stable emulsions but also structured liquids with various geometries by using extrusion printing and 3D printing techniques. By undergoing tribochemical reactions at its sulfonic terminus, the surfactant can endow the resultant emulsions with favorable lubricity even under high load-bearing conditions. Our study may provide new insights into creating complex liquid devices and new-generation lubricants capable of combining the characteristics of both liquid and solid lubricants.

Photozyme-Catalyzed ATP Generation Based on ATP Synthase-Reconstituted Nanoarchitectonics.

We demonstrate that ATP synthase-reconstituted proteoliposome coatings on the surface of microcapsules can realize photozyme-catalyzed oxidative phosphorylation. The microcapsules were assembled through layer-by-layer deposition of semiconducting graphitic carbon nitride (g-C3N4) nanosheets and polyelectrolytes. It is found that electrons from polyelectrolytes are transferred to g-C3N4 nanosheets, which enhances the separation of photogenerated electron-hole pairs. Thus, the encapsulated g-C3N4 nanosheets as the photozyme accelerate oxidation of glucose into gluconic acid to yield protons under light illumination. The outward transmembrane proton gradient is established to drive ATP synthase to synthesize adenosine triphosphate. With such an assembled system, light-driven oxidative phosphorylation is achieved. This indicates that an assembled photozyme can be used for oxidative phosphorylation, which creates an unusual way for chemical-to-biological energy conversion. Compared to conventional oxidative phosphorylation systems, such an artificial design enables higher energy conversion efficiency.

Small Molecules Mediated the Chirality Transfer in Self-Assembled Nanocomposites with Strong Circularly Polarized Luminescence.

Manipulation of the chirality at all scales has a cross-disciplinary importance and may address key challenges at the heart of physical sciences. One critical question in this field is how the chirality of one entity can be transferred to the asymmetry of another entity. Here, we find that small molecules play a crucial role in the chirality transfer from chiral organic molecules to CdSe/CdS nanorods, where the handedness of the nanorod assemblies either agrees or disagrees with that of the molecular assemblies, leading to the positive or inverse chirality transfer. The assembling mode of nanorods on the molecular assemblies, where the nanorods are either lying or standing, is closely associated with the handedness of the nanorod assemblies, resulting in opposite chirality. Furthermore, we have found that circularly polarized emission from chiral assemblies of nanorods is dependent on molecular additives. The promoted luminescence dissymmetry factor (glum) of the nanocomposites with a high value of ∼0.3 could be attained under optimal conditions.

Principles of Cation-π Interactions for Engineering Mussel-Inspired Functional Materials.

Supramolecular assembly is commonly driven by noncovalent interactions (e.g., hydrogen bonding, electrostatic, hydrophobic, and aromatic interactions) and plays a predominant role in multidisciplinary research areas ranging from materials design to molecular biology. Understanding these noncovalent interactions at the molecular level is important for studying and designing supramolecular assemblies in chemical and biological systems. Cation-π interactions, initially found through their influence on protein structure, are generally formed between electron-rich π systems and cations (mainly alkali, alkaline-earth metals, and ammonium). Cation-π interactions play an essential role in many biological systems and processes, such as potassium channels, nicotinic acetylcholine receptors, biomolecular recognition and assembly, and the stabilization and function of biomacromolecular structures. Early fundamental studies on cation-π interactions primarily focused on computational calculations, protein crystal structures, and gas- and solid-phase experiments. With the more recent development of spectroscopic and nanomechanical techniques, cation-π interactions can be characterized directly in aqueous media, offering opportunities for the rational manipulation and incorporation of cation-π interactions into the design of supramolecular assemblies. In 2012, we reported the essential role of cation-π interactions in the strong underwater adhesion of Asian green mussel foot proteins deficient in l-3,4-dihydroxyphenylalanine (DOPA) via direct molecular force measurements. In another study in 2013, we reported the experimental quantification and nanomechanics of cation-π interactions of various cations and π electron systems in aqueous solutions using a surface forces apparatus (SFA).Over the past decade, much progress has been achieved in probing cation-π interactions in aqueous solutions, their impact on the underwater adhesion and cohesion of different soft materials, and the fabrication of functional materials driven by cation-π interactions, including surface coatings, complex coacervates, and hydrogels. These studies have demonstrated cation-π interactions as an important driving force for engineering functional materials. Nevertheless, compared to other noncovalent interactions, cation-π interactions are relatively less investigated and underappreciated in governing the structure and function of supramolecular assemblies. Therefore, it is imperative to provide a detailed overview of recent advances in understanding of cation-π interactions for supramolecular assembly, and how these interactions can be used to direct supramolecular assembly for various applications (e.g., underwater adhesion). In this Account, we present very recent advances in probing and applying cation-π interactions for mussel-inspired supramolecular assemblies as well as their structural and functional characteristics. Particular attention is paid to experimental characterization techniques for quantifying cation-π interactions in aqueous solutions. Moreover, the parameters responsible for modulating the strengths of cation-π interactions are discussed. This Account provides useful insights into the design and engineering of smart materials based on cation-π interactions.

Wide-Temperature Flexible Supercapacitor from an Organohydrogel Electrolyte and Its Combined Electrode.

Hydrogel-based flexible supercapacitors possess the merits of highly ionic conductivity and superior power density, but the existence of water limits their application in extreme temperature scenarios. Noticeably, it is a challenge for people to design more extremely temperature adaptable systems for flexible supercapacitors based on hydrogels with a wide temperature region. In this work, a wide-temperature flexible supercapacitor that can operate at -20-80 °C was fabricated by an organohydrogel electrolyte and its combined electrode (also known as an electrode/electrolyte composite). Upon introducing highly hydratable LiCl into an ethylene glycol (EG)/H2 O binary solvent, owing to the ionic hydration effect of LiCl and the hydrogen bond interaction between EG and H2 O molecules, the organohydrogel electrolyte exhibits satisfactory resistance to freezing (freezing point of -113.9 °C), anti-drying capability (78.2 % of weight retention after vacuum drying at 60 °C for 12 h) and excellent ionic conductivity both at room temperature (13.9 mS cm-1 ) and low temperature (6.5 mS cm-1 after 31 days at -20 °C). By using organohydrogel electrolyte as binder, the prepared electrode/electrolyte composite effectively reduces interface impedance and enhances specific capacitance due to the uninterrupted ion transport channels and extended interface contact area. The assembled supercapacitor delivers a specific capacitance of 149 F g-1 , a power density of 160 W kg-1 , and an energy density of 13.24 Wh kg-1 at a current density of 0.2 A g-1 . The initial 100 % capacitance can be maintained after 2000 cycles at 1.0 A g-1 . More importantly, the specific capacitances can be well maintained even at -20 and 80 °C. With other advantages such as excellent mechanical property, the supercapacitor is an ideal power source suitable for various working conditions.

Cu2 P7 -CoP Heterostructure Nanosheets Enable High-Performance of 5-Hydroxymethylfurfural Electrooxidation.

Electrooxidation of 5-hydroxymethylfural (HMF) into 2,5-furandicarboxylicacid (FDCA) has been regarded as a promising sustainable approach to achieve value-added chemicals. However, it is still impeded by the unsatisfactory performance of electrocatalysts. Here, Cu2 P7 -CoP heterostructure nanosheets were reported to enable powerful HMF electrooxidation. The Cu2 P7 -CoP heterostructure nanosheets were fabricated by microwave-assisted deep eutectic solvent (DES) approach, along with subsequent phosphiding. The Cu2 P7 -CoP heterostructure nanosheets enabled a superb 100 % HMF conversion at 1.43 V (vs. RHE) with 98.8 % FDCA yield and 98 % Faradaic efficiency (FE), demonstrating its promising application in HMF electrooxidation. X-ray photoelectron spectroscopy (XPS) analysis, open-circuit potential (OCP) approach and density functional theory (DFT) calculation uncovered that the electron transfer and redistribution between Cu2 P7 and CoP improved the adsorption capacity of HMF and modulated the catalytic performance. This study not only offered a powerful electrocatalyst for HMF electrooxidation, but also provided a conceptually new strategy for the heterostructure catalyst design.

Macroporous Aerogels Using High Internal Phase Pickering Emulsions for Adsorption of Dyes.

The treatment of industrial printing and dyeing wastewater is the focus of the chemical environmental protection industry. Noticeably, the physical adsorption has attracted wide attention due to the selective dye adsorption, simple process, and convenient operation. New aerogels featuring low density and high porosity are regarded as ideal physical adsorption materials for sewage treatment. In this work, high internal phase Pickering emulsions were designed and prepared. The polysaccharide complex originating from sodium octenylsuccinate starch and chitosan serves as the stabilizer, water and hexane act as the external and internal phase, respectively. Acrylic acid was introduced into the external phase to initiate UV polymerization. The high internal phase Pickering emulsions as templates were removed through freeze-drying to produce aerogel materials with macroporous structures, the size of the pores: 43.54 ± 12.75 µm. The scanning electron microscopy (SEM) images show that the pore size of aerogel materials was similar to that of emulsion droplets, verifying the template role of emulsion in the polymerization process. In addition, aerogels possess good mechanical properties and can withstand a pressure of megapascal, exhibiting favorable stability when floating in water for a long time (6 months). Methyl violet, malachite green, methylene blue, and acridine orange in aqueous solution were selected as model dyes to explore the removal process and the mechanism. The adsorption was conformed to be the pseudo-second-order kinetic model and the Freundlich adsorption isotherm, namely, the dye adsorption of the aerogels was the multilayer adsorption on the uneven surface, and the mechanism of the adsorption was related to the π-π interaction.

Particle-Polymer Union with Changeable Wettability for Constructing Bijels Using a Simple Mixing Method.

Bicontinuous emulsion gels (bijels) are nonequilibrium dispersed systems with particle-stabilized continuous fluid domains, and the internal connectivity of channels brings the possibility of efficient mass transport, endowing bijels great potential in diverse applications. Different from the common method to produce bijels, the spinodal decomposition, which needs precise temperature control and is restricted by the selection of liquid pairs, in this work, a direct mixing method was performed to construct bijels, simplifying the fabrication process. The hydrophilic rod-shaped cellulose nanocrystalline (CNC) particles were in situ combined with the hydrophobic polymer, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2), to acquire a controllable interfacial wettability of CNC. The CNC@mPDMS-NH2 complexes were adsorbed at the water-toluene interface and achieved a change of Pickering emulsion types, oil-in-water, bijel, and water-in-oil, through tuning the interfacial performance of CNC@mPDMS-NH2 complexes. A three-dimensional scanning image and curvature calculation were applied to verify the obtained bijel, further demonstrating the successful preparation of the bicontinuous structure. This work enriched the members of particles for stabilizing bijels and was considered to be scalable in manufacturing for applications on a large scale.

Developing Safe Organohydrogel Sunscreens Using Polyelectrolyte-Betaine Surfactant Complexes.

Oil-in-water emulsions are extensively used in skincare products due to their improved texture, stability, and effectiveness. There is limited success in developing effective delivery systems that can selectively target the active sunscreen ingredients onto the skin surface. Herein, an organohydrogel was prepared by physical cross-linking of an oil-in-water nanoemulsion with chitosan under neutral pH conditions. In the presence of a small quantity of coconut oil, lauramidopropyl betaine and glycerol were able to emulsify the active sunscreen ingredients into nanoscale droplets with enhanced ultraviolet light absorption. A facile pH-triggered interfacial cross-linking approach was applied to transform the nanoemulsion into an organohydrogel sunscreen. Furthermore, the organohydrogel sunscreen displayed encouraging characteristics including efficient UV-blocking capacity, resistance to water, simple removal, and minimal skin penetration. This facile approach provides an effective pathway for scaling up the organohydrogels, which are highly suitable for the safe application of sunscreen.

Biologically Derived Nanoarchitectonic Coatings for the Engineering of Hemostatic Needles.

Bleeding after venipuncture could cause blood loss, hematoma, bruising, hemorrhagic shock, and even death. Herein, a hemostatic needle with antibacterial property is developed via coating of biologically derived carboxymethyl chitosan (CMCS) and Cirsium setosum extract (CsE). The rapid transition from films of the coatings to hydrogels under a wet environment provides an opportunity to detach the coatings from needles and subsequently seal the punctured site. The hydrogels do not significantly influence the healing process of the puncture site. After hemostasis, the coatings on hemostatic needles degrade in 72 h without inducing a systemic immune response. The composition of CMCS can inhibit bacteria of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus by destroying the membrane of bacteria. The hemostatic needle with good hemostasis efficacy, antibacterial property, and safety is promising for the prevention of bleeding-associated complications in practical applications.

Metal ions confinement defines the architecture of G-quartet, G-quadruplex fibrils and their assembly into nematic tactoids.

G-quadruplex, assembled from a square array of guanine (G) molecules, is an important structure with crucial biological roles in vivo but also a versatile template for ordered functional materials. Although the understanding of G-quadruplex structures is the focus of numerous studies, little is known regarding the control of G-quartet stacking modes and the spontaneous orientation of G-quadruplex fibrils. Here, the effects of different metal ions and their concentrations on stacking modes of G-quartets are elucidated. Monovalent cations (typically K+) facilitate the formation of G-quadruplex hydrogels with both heteropolar and homopolar stacking modes, showing weak mechanical strength. In contrast, divalent metal ions (Ca2+, Sr2+, and Ba2+) at given concentrations can control G-quartet stacking modes and increase the mechanical rigidity of the resulting hydrogels through ionic bridge effects between divalent ions and borate. We show that for Ca2+ and Ba2+ at suitable concentrations, the assembly of G-quadruplexes results in the establishment of a mesoscopic chirality of the fibrils with a regular left-handed twist. Finally, we report the discovery of nematic tactoids self-assembled from G-quadruplex fibrils characterized by homeotropic fibril alignment with respect to the interface. We use the Frank-Oseen elastic energy and the Rapini-Papoular anisotropic surface energy to rationalize two different configurations of the tactoids. These results deepen our understanding of G-quadruplex structures and G-quadruplex fibrils, paving the way for their use in self-assembly and biomaterials.

Self-assembly of fullerene C60-based amphiphiles in solutions.

Fullerene C60 is an all-carbon cage molecule with rich physicochemical properties. It is highly symmetric and hydrophobic, which can be used as a building block for the preparation of amphiphiles that self-assemble into diverse supramolecular structures in aqueous solutions. Meanwhile, C60 is also lipophobic, which is different from the alkyl chains in traditional surfactants. By attaching alkyl chains to the C60 sphere, a new type of lipophobic-lipophilic amphiphiles can be constructed which undergo self-assembly in n-alkanes. When inorganic clusters such as polyoxometalate are linked to the C60 sphere, organic-inorganic hybrids will be obtained which can self-assemble in polar organic solvents. Pristine C60 has also been modified by polar groups such as hydroxy and carboxy, which are linked to hydrophobic moieties and form a new class of amphiphiles. In this review, the self-assembly of C60-based amphiphiles in aqueous and nonaqueous solutions will be summarized. The characteristics exhibited by C60-based amphiphiles during the self-assembly will be discussed with close comparison to traditional surfactants, and the influences of the aggregate formation on the physicochemical properties of the C60 sphere will be described. Finally, a brief summary will be given together with a promising perspective in near future.

Dual-Driven Mechanically and Tribologically Adaptive Hydrogels Solely Constituted of Graphene Oxide and Water.

Although mythologies and fictions have recorded living creatures fully composed of inorganics, it is however hard to turn inorganic constituents into lifelike materials in reality as they usually do not possess characteristics required for constructing a living organism. Here, we report to our knowledge the first biomimetic hydrogel in response to both pH and temperature variations that solely comprises graphene oxide and water. The hydrogel is capable of abruptly and reversibly switching its mechanical and tribological properties by more than 10-fold and 5-fold magnitudes, respectively, as a result of pH- and/or thermal-induced topological reconfiguration of its internal microstructure and ordering. Such behavior closely mimics some natural living organisms such as muscles and sea cucumbers. The hydrogel also shows a low coefficient of friction at pH 2 and room temperature, indicating it a potent smart lubricant free of any flammable and toxic organic base oils and additives.

Development of Tough Thermoplastic Elastomers by Leveraging Rigid-Flexible Supramolecular Segment Interplays.

Supramolecular interactions facilitate the development of tough multifunctional thermoplastic elastomers. However, the fundamental principles that govern supramolecular toughening are barely understood, and the rational design to achieve the desired high toughness remains daunting. Herein, we report a simple and robust method for toughening thermoplastic elastomers by rationally tailoring hard-soft phase separation structures containing rigid and flexible supramolecular segments. The introduced functional segments with distinct structural rigidities provide mismatched supramolecular interactions to efficiently tune the energy dissipation and bear an external load. The optimal supramolecular elastomer containing aromatic amide and acylsemicarbazide moieties demonstrates a record toughness (1.2 GJ m-3 ), extraordinary crack tolerance (fracture energy 282.5 kJ m-2 ), an ultrahigh true stress at break (2.3 GPa), good elasticity, healing ability, recyclability, and impact resistance. The toughening mechanism is validated by testing various elastomers, confirming the potential for designing and developing super-tough supramolecular materials with promising applications in aerospace and electronics.

Engineering Poly(ethylene glycol) Nanoparticles for Accelerated Blood Clearance Inhibition and Targeted Drug Delivery.

Surface modification with poly(ethylene glycol) (PEGylation) is an effective strategy to improve the colloidal stability of nanoparticles (NPs) and is often used to minimize cellular uptake and clearance of NPs by the immune system. However, PEGylation can also trigger the accelerated blood clearance (ABC) phenomenon, which is known to reduce the circulation time of PEGylated NPs. Herein, we report the engineering of stealth PEG NPs that can avoid the ABC phenomenon and, when modified with hyaluronic acid (HA), show specific cancer cell targeting and drug delivery. PEG NPs cross-linked with disulfide bonds are prepared by using zeolitic imidazolate framework-8 NPs as templates. The reported templating strategy enables the simultaneous removal of the template and formation of PEG NPs under mild conditions (pH 5.5 buffer). Compared to PEGylated liposomes, PEG NPs avoid the secretion of anti-PEG antibodies and the presence of anti-PEG IgM and IgG did not significantly accelerate the blood clearance of PEG NPs, indicating the inhibition of the ABC effect for the PEG NPs. Functionalization of the PEG NPs with HA affords PEG NPs that retain their stealth properties against macrophages, target CD44-expressed cancer cells and, when loaded with the anticancer drug doxorubicin, effectively inhibit tumor growth. The innovation of this study lies in the engineering of PEG NPs that can circumvent the ABC phenomenon and that can be functionalized for the improved and targeted delivery of drugs.