Advances in biomimetic nanomaterial delivery systems: harnessing nature's inspiration for targeted drug delivery.

The properties of nanomaterials make them promising and advantageous for use in drug delivery systems, but challenges arise from the immune system's recognition of exogenous nanoparticles, leading to their clearance and reduced targeting efficiency. Drawing inspiration from nature, this paper explores biomimetic strategies to transform recognizable nanomaterials into a "camouflaged state." The focal point of this paper is the exploration of bionic nanoparticles, with a focus on cell membrane-coated nanoparticles. These biomimetic structures, particularly those mimicking red blood cells (RBCs), white blood cells (WBCs), platelets, and cancer cells, demonstrate enhanced drug delivery efficiency and prolonged circulation. This article underscores the versatility of these biomimetic structures across diverse diseases and explores the use of hybrid cell membrane-coated nanoparticles as a contemporary trend. This review also investigated exosomes and protein bionic nanoparticles, emphasizing their potential for specific targeting, immune evasion, and improved therapeutic outcomes. We expect that this continued development based on biomimetic nanomaterials will contribute to the efficiency and safety of disease treatment.

Promoting C-C coupling for CO2 reduction on Cu2O electrocatalysts with atomically dispersed Rh atoms.

Cu2O doped with atomically dispersed Rh (Rh:Cu2O) is synthesized with a wet chemical method. It shows higher activity and faradaic efficiency at lower overpotential for reduction of CO2 to C2+ products, especially C2H4, than pristine Cu2O. We found that introducing Rh promotes CO2 adsorption, *CO hydrogenation to *CHO and their coupling to O*CCHO intermediates, which contributes to enhanced catalytic performance.

A Coupled System of Ni3S2 and Rh Complex with Biomimetic Function for Electrocatalytic 1,4-NAD(P)H Regeneration.

NAD(P)H cofactor is a critical energy and electron carrier in biocatalysis and photosynthesis, but the artificial reduction of NAD(P)+ to regenerate bioactive 1,4-NAD(P)H with both high activity and selectivity is challenging. Herein, we found that a coupled system of a Ni3S2 electrode and a Rh complex in an electrolyte (denoted as Ni3S2-Rh) can catalyze the reduction of NAD(P)+ to 1,4-NAD(P)H with superior activity and selectivity. The optimized selectivity in 1,4-NADH can be up to 99.1%, much higher than that for Ni3S2 (80%); the normalized activity of Ni3S2-Rh is about 5.8 times that of Ni3S2 and 13.2 times that of the Rh complex. The high performance of Ni3S2-Rh is attributed to the synergistic effect between metal sulfides and Rh complex. The NAD+ reduction reaction proceeds via a concerted electron-proton transfer (CEPT) mechanism in the Ni3S2-Rh system, in which Ni3S2 acts as a proton and electron-transfer mediator to accelerate the formation of Rh hydride (Rh-H), and then the Rh-H regioselectively transfers the hydride to NAD+ to form 1,4-NADH. The artificial system Ni3S2-Rh essentially mimics the functions of ferredoxin-NADP+ reductase in nature.

Natural Underwater Bioadhesive Offering Cohesion Modulation via Hydrogen Bond Disruptor: A Highly Injectable and in Vivo Stable Remedy for Gastric Ulcer Resolution.

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.

Bioinspired Multiscale Mineralization: From Fundamentals to Potential Applications.

The wondrous and imaginative designs of nature have always been an inexhaustible treasure trove for material scientists. Throughout the long evolutionary process, biominerals with hierarchical structures possess some specific advantages such as outstanding mechanical properties, biological functions, and sensing performances, the formation of which (biomineralization) is delicately regulated by organic component. Provoked by the subtle structures and profound principles of nature, bioinspired functional minerals can be designed with the participation of organic molecules. Because of the designable morphology and functions, multiscale mineralization has attracted more and more attention in the areas of medicine, chemistry, biology, and material science. This review provides a summary of current advancements in this extending topic. The mechanisms underlying mineralization is first concisely elucidated. Next, several types of minerals are categorized according to their structural characteristic, as well as the different potential applications of these materials. At last, a comprehensive overview of future developments for bioinspired multiscale mineralization is given. Concentrating on the mechanism of fabrication and broad application prospects of multiscale mineralization, the hope is to provide inspirations for the design of other functional materials.

Hydrogel-Based Biosensors for Bacterial Infections.

Hydrogels are known to have the advantages such as good biodegradability, biocompatibility, and easy functionalization, making them ideal candidates for biosensors. Hydrogel-based biosensors that respond to bacteria-induced microenvironmental changes such as pH, enzymes, antigens, etc., or directly interact with bacterial surface receptors, can be applied for early diagnosis of bacterial infections, providing information for timely treatment while avoiding antibiotic abuse. Furthermore, hydrogel biosensors capable of both bacteria diagnosis and treatment will greatly facilitate the development of point-of-care monitoring of bacterial infections. In this review, the recent advancement of hydrogel-based biosensors for bacterial infection is summarized and discussed. First, the biosensors based on pH-sensitive hydrogels, bacterial-specific secretions-sensitive hydrogels, and hydrogels directly in contact with bacterial surfaces are presented. Next, hydrogel biosensors capable of detecting bacterial infection in the early stage followed by immediate on-demand treatment are discussed. Finally, the challenges and future development of hydrogel biosensors for bacterial infections are proposed.

A Drop-By-Drop Self-Assembled All-Natural Hydrogel as a Desensitizer for Rapid and Enduring Management of Dentin Hypersensitivity.

Dentin hypersensitivity (DH) is a prevalent dental condition arising from the exposure of dentin tubules (DTs), leading to discomfort upon external stimuli. However, achieving swift and profound occlusion of these exposed DTs for immediate and enduring relief remains challenging due to the intricate dentin structure and oral environment. Herein, a pioneering and facile drop-by-drop strategy involving an in situ generated natural supramolecular hydrogel formed by self-assembling silk fibroin (SF) and tannic acid (TA) within the narrow DT space is proposed. When SF and TA aqueous solutions are applied successively to exposed dentin, they penetrate deeply within DTs and coassemble into compact gels, robustly adhering to DT walls. This yields a rapid and compact occlusion effect with an unprecedented depth exceeding 250 µm, maintaining stable occlusion efficacy even under rigorous in vitro and in vivo erosion and friction conditions for no less than 21 days. Furthermore, the biocompatibility and effective occlusion properties are verified through cell studies in simulated oral settings and an in vivo rabbit model. This study, for the first time, demonstrates the translational potential of hydrogel-based desensitizers in treating DH with prompt action, superior occlusion depth and enduring treatment benefits, holding promise as clinical-friendly restorative solutions for delicate-structured biosystems.

The application of a multi-component reaction peptide as a model regenerative active to enhance skin wound-healing postlaser procedure in a double-blinded placebo-controlled clinical trial.

INTRODUCTION: Esthetic procedures are currently among the most effective options for consumers seeking to correct aging signs such as fine lines, wrinkles, and skin tone unevenness. Currently, there is a scientific need for an adjunct active to be paired with esthetic procedures to encourage wound recovery and address postprocedure pigmentation concerns. OBJECTIVE: Toward that goal, this study assessed the efficacy of a peptide created from a multi-component reaction (multi-component peptide, MCP) as a model active for postprocedure care and evaluated its ability to promote skin healing in an ablative laser-induced wound model on the forearm. METHODS: The mechanism of action of MCP was investigated using tubo assays, 2D melanocyte, and fibroblast cultures, reconstructed skin equivalents, and ex vivo skin explants. The MCP formula and the clinical benchmark formula of Aquaphor were assessed head-to-head by applying the products topically in an ablative laser-induced wound model (n = 20 subjects). The promotion of wound healing was evaluated by the investigator assessment of epithelial confluence, crusting or scabbing, general wound appearance, erythema, and edema. RESULTS: MCP was determined to be beneficial to postprocedure skin recovery and healing by four main mechanisms of action: barrier repair as determined in an ex vivo tape-stripping model, reduction of inflammation and postinflammatory hyperpigmentation, reduction of elastase activity, and stimulation of fibroblast through the mTOR pathway. The formula containing 10% MCP enhanced the kinetics of epithelial confluence and improvement of the crusting or scabbing appearance of the laser-generated wounds in a laser-induced mini-zone wound healing study on the forearm. CONCLUSION: This study demonstrates the use of MCP as a proof of concept regenerative active that when incorporated into an optimized postprocedure skincare formula can improve skin healing and enhance the appearance of skin after injury with relevance to ablative aesthetic procedures.

Light and Magnetism Orchestrating Aquatic Pollutant-Degradation Robots in Programmable Trajectories.

Interfacial floating robots have promising applications in carriers, environmental monitoring, water treatment, and so on. Even though, engineering smart robots with both precisely efficient navigation and elimination of water pollutants in long term remains a challenge, as the superhydrophobicity greatly lowers resistance for aquatic motion while sacrificing chemical reactivity of the surface. Here, a pollutant-removing superhydrophobic robot integrated with well-assembled iron oxide-bismuth sulfide heterojunction composite minerals, which provide both light and magnetic propulsion, and the ability of catalytic degradation, is reported. The motion velocity of the robot reaches up to 51.9 mm s-1 within only 300 ms of acceleration under the orchestration of light, and brakes rapidly (≈200-300 ms) once turn off the light. And magnetism extends the robot to work in broad range of surface tensions in any programmable trajectory. Besides, purification of polluted water is efficiently achieved in situ and the degradation efficiency exhibits eightfold enhancements under the effect of light-triggered photothermal behavior coupled with magnetic induction, overcoming the dilemma of efficient motion with catalytic superhydrophobicity. This strategy developed here provides guidelines for the explorations of high-performance smart devices.

A hydrogel gripper enabling fine movement based on spatiotemporal mineralization.

Fine tailoring of the subtle movements of a hydrogel actuator through simple methods has widespread application prospects in wearable electronics, bionic robots and biomedical engineering. However, to the best of our knowledge, this challenge is not yet completed. Inspired by the diffusion-reaction process in nature, a hydrogel gripper with the capability of fine movement was successfully prepared based on the spatiotemporal fabrication of the polypyrrole (PPY) pattern in a poly (N-isopropylacrylamide) (PNIPAM) hydrogel. The hydrogel was given gradient porous structures using a one-step UV irradiation method. Moreover, photothermal PPY patterns on the hydrogel were obtained through spatiotemporal mineralization of ferric hydroxide followed by the polymerization of pyrrole in a controllable manner. Taking advantage of the unique structures, the hydrogel gripper can not only achieve reversible grasping-releasing of substrates with the tuning of temperature (similar to that of hands), but also generate delicate movement under the irradiation of light (resembling that of finger joints). The strategy reported here is easily accessible and there is no need for sophisticated templates, therefore making it superior to other existing methods. We believe this work will provide references for the design and application of more advanced soft actuators.

Supramolecular Self-Healing Antifouling Coating for Dental Materials.

In orthodontic treatment, orthodontic appliances are prone to bacterial infections, which pose a risk to oral health. Surface modification of orthodontic appliances has been explored to improve their antifouling properties and impart antibacterial capabilities, inhibiting initial bacterial adhesion and biofilm formation. However, coatings are susceptible to damage in the complex oral environment, leading to a loss of functionality. Here, we have prepared an antifouling self-healing coating based on supramolecular bonding by employing a simple spin coating method. The presence of the hydrophilic zwitterionic trimethylamine N-oxide (TMAO) and the hydrophobic antimicrobial moieties triclosan acrylate (TCSA) imparts to the polymers an amphiphilic structure and enhances the interaction with bacteria, resulting in excellent antimicrobial activity and surface antifouling properties. The multiple hydrogen bonds of ureido-pyrimidinone methacrylate (UPyMA) and ionic interactions contained in the polymers not only increased the adhesion of the coating to the material substrate (approximately 3 times) but also endowed the coating with the intrinsic self-healing ability to restore the antibiofouling properties at oral temperature and humidity. Finally, the polymer coating is biologically safe both in vitro and in vivo, showing no cytotoxic effects on cells and tissues. This research offers a promising avenue for improving the performance of orthodontic appliances and contributes to the maintenance and treatment of oral health.

Mimicking Antioxidases and Hyaluronan Synthase: A Zwitterionic Nanozyme for Photothermal Therapy of Osteoarthritis.

Restoring joint homeostasis is crucial for relieving osteoarthritis (OA). Current strategies are limited to unilateral efforts in joint lubrication, inhibition of inflammation, free radicals scavenging, and cartilage regeneration. Herein, by modifying molybdenum disulfide (MoS2 ) with Mg2+ -doped polydopamine and coating with polysulfobetaines, a dual-bionic photothermal nanozyme (MPMP) is constructed to mimic antioxidases/hyaluronan synthase for OA therapy. Photothermally enhanced lubrication lowers the coefficient of friction (0.028) in the early stage of OA treatment. The antioxidases-mimicking properties of MPMP nanozyme contribute to eliminating reactive oxygen and nitrogen species (ROS/RNS) (over 90% of scavenging ratio for H2 O2 /·OH/O· 2 - /DPPH/ABTS+ ) and supplying O2 . With NIR irradiation, the MPMP nanozyme triggers thermogenesis (upregulating HSP70 expression) and Mg2+ release, which promotes the chondrogenesis in inflammatory conditions by deactivating NF-κB/IL-17 signaling pathways and enhancing MAPK signaling pathway. Benefiting from HSP70 and Mg2+ , MPMP-NIR shows HAS-mimicking activity to increase the intracellular (twofold) and extracellular (3.12-fold) HA production. Therefore, MPMP-NIR demonstrates superior spatiotemporally therapeutic effect on OA in mice model, in terms of osteophytes (83.41% of reduction), OARSI scores (88.57% of reduction), and ACAN expression (2.70-fold of increment). Hence, insights into dual-bionic nanozymes can be a promising strategy for OA therapy or other inflammation-related diseases.

Akkermansia muciniphila and Bifidobacterium bifidum Prevent NAFLD by Regulating FXR Expression and Gut Microbiota.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods: Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results: Both strains were able to attenuate mass gain (p<0.001), insulin resistance (p<0.001), and liver lipid deposition (p<0.001). They also reduced the levels of the pro-inflammatory factors (p<0.05) and the proportion of Th17 (p<0.001), while elevating the proportion of Treg (p<0.01). Both strains activated hepatic FXR while suppressing intestinal FXR (p<0.05), and elevating tight junction protein expression (p<0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions: Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.

Characterization of an ablative fractional CO2 laser-induced wound-healing model based on in vitro 3D reconstructed skin.

OBJECTIVE: This study describes the development and characterization of a novel in vitro wound-healing model based on a full-thickness reconstructed skin by exposing the tissue to fractional ablative laser treatment. METHOD: A 3D full-thickness skin model was fabricated and treated with fractional ablative CO2 laser. Wound-healing process was characterized by HE staining, noninvasive OCT imaging, immunostaining, as well as transepidermal water loss measurement. Cytokines and proteins involved in the inflammatory and dermal remodeling process were studied by ELISA and protein array assays. RESULTS: Fractional ablative CO2 treatment induced a wound zone of 9 mm in diameter, containing 56 micro-wounds with 200 µm diameter and 500-700 µm in depth on reconstructed full-thickness skin model. HE staining revealed a typical wound morphology and healing process with migration of keratinocytes, formation and extrusion of necrotic tissue, and cell inclusion in dermis, which correlates with clinical observations. Based on OCT and TEWL measurements, the re-epithelialization took place over 2 days. Laser-triggered keratinocytes proliferation and differentiation were demonstrated by activated Ki67 and Filaggrin expression respectively. Injury-invoked cytokine ICAM-1 showed instant upregulation on Day 1. Decreased epidermis thickness and depression of IGFBP-2 protein level synergistically indicated the unavoidable thermal side effects from laser treatment. Downregulated DKK-1 protein level and upregulation of α-SMA together implicated the risk of potential fibrosis post-laser treatment. CONCLUSION: This in vitro laser wounded reconstructed skin model captured the key events of wound-healing process, could be used to investigate the mechanisms of wound-healing triggered by a commonly used beauty procedure, and also provides a valuable tool for evaluating the efficacy of novel actives for the post-procedure application.

Supramolecular Photonic Hydrogel for High-Sensitivity Alkaline Phosphatase Detection via Synergistic Driving Force.

Structurally-colored photonic hydrogels which are fabricated by introducing hydrogels into thin films or photonic crystal structures are promising candidates for biosensing. Generally, the design of photonic hydrogel biosensors is based on the sensor-analyte interactions induced charge variation within the hydrogel matrix, or chemically grafting binding sites onto the polymer chains, to achieve significant volume change and color variation of the photonic hydrogel. However, relatively low anti-interference capability or complicated synthesis hinder the facile and low-cost fabrication of high-performance photonic hydrogel biosensors. Here, a facilely prepared supramolecular photonic hydrogel biosensor is developed for high-sensitivity detection of alkaline phosphatase (ALP), which is an extensively considered clinical biomarker for a variety of diseases. Responding to ALP results in the broken supramolecular crosslinking and thus increased lattice distancing of the photonic hydrogel driven by synergistic repulsive force between nanoparticles embedded in photonic crystal structure and osmotic swelling pressure. The biosensor shows sensitivity of 7.3 nm spectral shift per mU mL-1 ALP, with detection limit of 0.52 mU mL-1 . High-accuracy colorimetric detection can be realized via a smartphone, promoting point-of-care sensing and timely diagnosis of related pathological conditions.

Chitosan based photothermal scaffold fighting against bone tumor-related complications: Recurrence, infection, and defects.

After bone tumor resection, the severe complications including cancer recurrence, infection and extensive bone loss are still a challenge. To address this problem, a chitosan/hydroxypropyltrimethyl ammonium chloride chitosan/hydroxyapatite/black phosphorus (CS/HC/HA/BP) hybrid photothermal scaffold with a multistage photothermal strategy was developed. HC-stabilized BP endowed the scaffold with simultaneous antitumor/antibacterial properties under photothermal stimulation of <50 °C. Subsequently, excellent osteogenesis could be achieved with mild hyperthermia stimulation (∼42 °C) through up-regulating the expressions of heat shock proteins. Under NIR irradiation, the scaffold could eliminate 95 % of osteosarcoma cells as well as 97 % of E. coli and 92 % of S. aureus. The osteogenic gene expressions of ALP, COL 1A1, and OCN in photothermal group were 1.64, 1.31 and 1.27 folds higher than that of non-photothermal group in vivo, respectively. Therefore, the obtained scaffold synergized with multistage photothermal strategy was effective and a reference for the treatment of other complex diseases.

Recent advancements in wound management: Tailoring superwettable bio-interfaces.

Skin tissue suffering from severe damages fail in self-regeneration. Proper wound dressings are highly demanded to protect the wound region and accelerate the healing process. Although large efforts have been devoted, there still exist disturbing dilemmas for traditional dressings. The exquisite design of bio-interface upon superwettable materials opens new avenues and addresses the problems perfectly. However, the advancements in this area have rarely been combed. In light of this, this minireview attempts to summarize recent strategies of superwettable bio-interfaces for wound care. Concentrating on the management of biofluids (blood and exudate), we described superwettable hemostatic bio-interfaces first, and then introduced the management of exudates. Finally, the perspective of this area was given. This minireview gives a comprehensive outline for readers and is believed to provide references for the design of superwettable materials in biomedical area.

Electrocatalytic NAD+ reduction via hydrogen atom-coupled electron transfer.

Nicotinamide adenine dinucleotide cofactor (NAD(P)H) is regarded as an important energy carrier and charge transfer mediator. Enzyme-catalyzed NADPH production in natural photosynthesis proceeds via a hydride transfer mechanism. Selective and effective regeneration of NAD(P)H from its oxidized form by artificial catalysts remains challenging due to the formation of byproducts. Herein, electrocatalytic NADH regeneration and the reaction mechanism on metal and carbon electrodes are studied. We find that the selectivity of bioactive 1,4-NADH is relatively high on Cu, Fe, and Co electrodes without forming commonly reported NAD2 byproducts. In contrast, more NAD2 side product is formed with the carbon electrode. ADP-ribose is confirmed to be a side product caused by the fragmentation reaction of NAD+. Based on H/D isotope effects and electron paramagnetic resonance analysis, it is proposed that the formation of NADH on these metal electrodes proceeds via a hydrogen atom-coupled electron transfer (HadCET) mechanism, in contrast to the direct electron-transfer and NAD˙ radical pathway on carbon electrodes, which leads to more by-product, NAD2. This work sheds light on the mechanism of electrocatalytic NADH regeneration, which is different from biocatalysis.

Chloroplast-inspired Scaffold for Infected Bone Defect Therapy: Towards Stable Photothermal Properties and Self-Defensive Functionality.

Bone implant-associated infections induced by bacteria frequently result in repair failure and threaten the health of patients. Although black phosphorus (BP) material with superior photothermal conversion ability is booming in the treatment of bone disease, the development of BP-based bone scaffolds with excellent photothermal stability and antibacterial properties simultaneously remains a challenge. In nature, chloroplasts cannot only convert light into chemical energy, but also hold a protective and defensive envelope membrane. Inspired by this, a self-defensive bone scaffold with stable photothermal property is developed for infected bone defect therapy. Similar to thylakoid and stroma lamella in chloroplasts, BP is integrated with chitosan and polycaprolactone fiber networks. The mussel-inspired polydopamine multifunctional "envelope membrane" wrapped above not only strengthens the photothermal stability of BP-based scaffolds, but also realizes the in situ anchoring of silver nanoparticles. Bacteria-triggered infection of femur defects in vivo can be commendably inhibited at the early stage via these chloroplast-inspired implants, which then effectively promotes endogenous repair of the defect area under mild hyperthermia induced by near-infrared irradiation. This chloroplast-inspired strategy shows outstanding performance for infected bone defect therapy and provides a reference for the functionality of other biomedical materials.

Understanding the factors governing the water oxidation reaction pathway of mononuclear and binuclear cobalt phthalocyanine catalysts.

The rational design of efficient catalysts for electrochemical water oxidation highly depends on the understanding of reaction pathways, which still remains a challenge. Herein, mononuclear and binuclear cobalt phthalocyanine (mono-CoPc and bi-CoPc) with a well-defined molecular structure are selected as model electrocatalysts to study the water oxidation mechanism. We found that bi-CoPc on a carbon support (bi-CoPc/carbon) shows an overpotential of 357 mV at 10 mA cm-2, much lower than that of mono-CoPc/carbon (>450 mV). Kinetic analysis reveals that the rate-determining step (RDS) of the oxygen evolution reaction (OER) over both electrocatalysts is a nucleophilic attack process involving a hydroxy anion (OH-). However, the substrate nucleophilically attacked by OH- for bi-CoPc is the phthalocyanine cation-radical species (CoII-Pc-Pc˙+-CoII-OH) that is formed from the oxidation of the phthalocyanine ring, while cobalt oxidized species (Pc-CoIII-OH) is involved in mono-CoPc as evidenced by the operando UV-vis spectroelectrochemistry technique. DFT calculations show that the reaction barrier for the nucleophilic attack of OH- on CoII-Pc-Pc˙+-CoII-OH is 1.67 eV, lower than that of mono-CoPc with Pc-CoIII-OH nucleophilically attacked by OH- (1.78 eV). The good agreement between the experimental and theoretical results suggests that bi-CoPc can effectively stabilize the accumulated oxidative charges in the phthalocyanine ring, and is thus bestowed with a higher OER performance.