Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

Versatile CO2-responsive Sponges Decorated with ZIF-8 for Bidirectional Separation of Oil/Water and Controllable Removal of Dyes.

The complex wastewater containing water-soluble dyes and water-insoluble oils has given rise to significant environmental concerns that demand urgent remediation. Herein, a novel "smart" multifunctional sponge (ZIF-8@PMS) stepwise decorated with ZIF-8 nanoparticles and CO2-responsive copolymer (poly(2-(diethylamino) ethyl methacrylate-co-3-(trimethoxysilyl)propyl acrylate-co-stearyl methacrylate) was successfully prepared for CO2 controllable oil/water separation and dyes removal. The results revealed that the sponge coated with CO2-responsive copolymer for three cycles (ZIF-8@PMS-3) exhibited optimal comprehensive properties. The ZIF-8@PMS-3 had excellent compressive-resilient characteristics and chemical stability. As expected, it displayed tunable wettability and charged state under the regulation of CO2. Based on these features, ZIF-8@PMS-3 presented highly efficient removal of oil and dyes, even for the dye-containing oil/water emulsions, via a synergistic combination of adsorption and separation methods. The adsorption capacity for oil and various organic solvents ranged from 21.3 to 50 g g-1. The maximum adsorption capacities toward anionic dyes: methyl orange with 1205.89 mg g-1 and methyl blue with 880.00 mg g-1 in the presence of CO2 through electrostatic interaction. In the absence of CO2, it achieved maximum adsorption capacities for cationic dyes, including malachite green with 1246.15 mg g-1 and rhodamine B with 203 mg g-1, primarily driven by π-π interactions. According to distinct adsorption mechanisms, ZIF-8@PMS-3 could selectively adsorb either anionic or cationic dyes by exploiting CO2 as a trigger. Furthermore, the separation efficiencies for both types of oil/water emulsions surpassed 99.9%, with respective fluxes of 1566.99 L m-2 h-1 (water-in-oil emulsion) and 310.37 L m-2 h-1 (oil-in-water emulsion). Additionally, the as-prepared sponges exhibited remarkable antibacterial properties and exceptional recyclability. Therefore, the ZIF-8@PMS-3 holds substantial promise for potential applications in practical industrial wastewater treatment.

Supramolecular nanoarchitectonics of phenolic-based nanofiller for controlled diffusion of versatile drugs in hydrogels.

Drug-dependent design of hydrogels is currently required for engineering the controlled release of therapeutics, which is a major contributor to the technical challenges relating to the clinical translation of hydrogel-drug systems. Herein, by integrating supramolecular phenolic-based nanofillers (SPFs) into hydrogel microstructures we developed a facile strategy to endow a range of clinically relevant hydrogels with controlled release properties for diverse therapeutic agents. The assembly of multiscale SPF aggregates leads to tunable mesh size and multiple dynamic interactions between SPF aggregates and drugs, which relaxes the available choices of drugs and hydrogels. This simple approach allowed for the controlled release of 12 representative drugs evaluated with 8 commonly used hydrogels. Moreover, the anesthetic drug lidocaine was loaded into SPF-integrated alginate hydrogel and demonstrated sustained release for 14 days in vivo, validating the potential for long-term anesthesia in patients.

Customizable Supraparticles Constructed from Catechol-Terminated Molecular Building Blocks with Controllable Intermolecular Interactions.

Colloidal supraparticles integrated with multicomponent primary particles come with emerging or synergetic functionalities. However, achieving the functional customization of supraparticles remains a great challenge because of the limited options of building blocks with tailorability and functional extensibility. Herein, we developed a universal approach to construct customizable supraparticles with desired properties from molecular building blocks obtained by the covalent conjugation of catechol groups with a series of orthogonal functional groups. These catechol-terminated molecular building blocks can assemble into primary particles driven by various intermolecular interactions (i.e. metal-organic coordination, host-guest, and hydrophobic interactions), and then further assemble into supraparticles governed by catechol-mediated interfacial interactions. Our strategy enables the formation of supraparticles with diverse functionalities, such as dual-pH responsiveness, light-controllable permeability, and non-invasive fluorescence labeling of living cells. The ease with which these supraparticles can be fabricated, and the ability to tailor their chemical and physical properties through the choice of metals and orthogonal functional groups used, should enable a variety of applications.

Systemic Tumor Suppression via Macrophage-Driven Automated Homing of Metal-Phenolic-Gated Nanosponges for Metastatic Melanoma.

Cell-based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug-loading with high accumulations in solid tumors. Herein, a tumor-targeting cellular drug delivery system (MAGN) by surface engineering of tumor-homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron-tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the "ON-OFF" gating effect of the polyphenol-based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor-targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs.

Intratumoral synthesis of transformable metal-phenolic nanoaggregates with enhanced tumor penetration and retention for photothermal immunotherapy.

Rationale: Effective photothermal therapy (PTT) remains a great challenge due to the difficulties of delivering photothermal agents with both deep penetration and prolonged retention at tumor lesion spatiotemporally. Methods: Here, we report an intratumoral self-assembled nanostructured aggregate named FerH, composed of a natural polyphenol and a commercial iron supplement. FerH assemblies possess size-increasing dynamic kinetics as a pseudo-stepwise polymerization from discrete nanocomplexes to microscale aggregates. Results: The nanocomplex can penetrate deeply into solid tumors, followed by prolonged retention (> 6 days) due to the in vivo growth into nanoaggregates in the tumor microenvironment. FerH performs a targeting ablation of tumors with a high photothermal conversion efficiency (60.2%). Importantly, an enhanced immunotherapeutic effect on the distant tumor can be triggered when co-administrated with checkpoint-blockade PD-L1 antibody. Conclusions: Such a therapeutic approach by intratumoral synthesis of metal-phenolic nanoaggregates can be instructive to address the challenges associated with malignant tumors.

A single-cell nanocoating of probiotics for enhanced amelioration of antibiotic-associated diarrhea.

The gut microbiota represents a large community of microorganisms that play an important role in immune regulation and maintenance of homeostasis. Living bacteria receive increasing interest as potential therapeutics for gut disorders, because they inhibit the colonization of pathogens and positively regulate the composition of bacteria in gut. However, these treatments are often accompanied by antibiotic administration targeting pathogens. In these cases, the efficacy of therapeutic bacteria is compromised by their susceptibility to antibiotics. Here, we demonstrate that a single-cell coating composed of tannic acids and ferric ions, referred to as 'nanoarmor', can protect bacteria from the action of antibiotics. The nanoarmor protects both Gram-positive and Gram-negative bacteria against six clinically relevant antibiotics. The multiple interactions between the nanoarmor and antibiotic molecules allow the antibiotics to be effectively absorbed onto the nanoarmor. Armored probiotics have shown the ability to colonize inside the gastrointestinal tracts of levofloxacin-treated rats, which significantly reduced antibiotic-associated diarrhea (AAD) resulting from the levofloxacin-treatment and improved some of the pre-inflammatory symptoms caused by AAD. This nanoarmor strategy represents a robust platform to enhance the potency of therapeutic bacteria in the gastrointestinal tracts of patients receiving antibiotics and to avoid the negative effects of antibiotics in the gastrointestinal tract.

Self-assembly of nanomicelles with rationally designed multifunctional building blocks for synergistic chemo-photodynamic therapy.

Rationale: The combination of photosensitizers, oxygen supply agents, and adjuvant therapy drugs in a single nano-drug delivery system for photodynamic therapy (PDT) has been showing great promises to overcome the inherent challenges of PDT for tumor treatment. However, the complicated preparation of integrating multiple components hampers their further developments. Here, we describe a self-assembly nanomicelle with rationally designed building blocks, which shows a high efficiency of synergistic chemo-photodynamic therapy in the animal modal. Methods: The nanomicelle was prepared by a coordination-driven self-assembly based on a rationally designed ferrocene cyclopalladated compound coupled with photosensitizers and hyaluronic acid (referred to as FCP-Tph/HA). The morphology, targeting drug delivery, pharmacokinetics, hemolysis, and multimodal synergistic therapy of FCP-Tph/HA were investigated. Results: The formation of nanomicelles presents a low hemolysis rate and a prolonged blood circulation time. FCP-Tph/HA possesses an enhanced antitumor effect in vitro through the specific binding of HA to CD44 and combining chemotherapy with oxygen self-supplying PDT. Simultaneously, the nanomicelle facilitates a significantly improved antitumor efficacy (>90% tumor regression) on a breast cancer model in vivo. Conclusion: Our results present a modular self-assembled nanomicellar platform with synergistic chemo-photodynamic therapy for challenging PDT-based tumor treatment.

CO2-responsive functional cotton fibers decorated with Ag nanoparticles for "smart" selective and enhanced dye adsorption.

Novel Ag nanoparticles (NPs) decorated CO2-responsive cotton fiber (PCCF@Ag) as eco-friendly adsorbent was prepared via in-situ growth of Ag NPs on the poly(2-(dimethylamino) ethyl methacrylate-co-4-acryloyloxybenzophenone) coated cotton fiber. The as-prepared PCCF@Ag displayed excellent adsorption performance toward both anionic and cationic dyes with or without CO2 stimulation, even under a wide range of pH from 3 to 11. The maximum adsorption capacities of the as-prepared PCCF@Ag toward anionic dye (1538.5 mg g-1 for MO) and cationic dyes (944.0 mg g-1 for MEB and 415.6 mg g-1 for NR) were satisfactory. The adsorption processes were described better by the Langmuir isotherm and pseudo-second-order kinetic models, respectively. Notably, upon CO2 stimulation, the PCCF@Ag exhibited significantly enhanced adsorption capacity toward anionic dyes, following ultrafast adsorption rate, which made the PCCF@Ag could selectively adsorb anionic dyes from mixture because of greatly different adsorption rates between anionic dyes (adsorption equilibrium within 2 min) and cationic dyes (adsorption equilibrium over 12 h). Additionally, the PCCF@Ag could maintain over 91.0% of adsorption capacity even after ten cycles, indicating its outstanding reusability. Meanwhile, the as-obtained PCCF@Ag exhibited excellent antibacterial activity. Overall, the as-obtained PCCF@Ag could be considered as a promising dye scavenger for wastewater remediation.

Pentagalloylglucose reduces AGE-induced inflammation by activating Nrf2/HO-1 and inhibiting the JAK2/STAT3 pathway in mesangial cells.

Pentagalloylglucose (PGG), a gallotannin polyphenolic compound, has been found to possess a host of beneficial pharmacologic activities, such as anti-inflammatory and antioxidative activities. We previously demonstrated that PGG is capable of binding to the cell membrane of renal mesangial cells, but the pharmacological effect of PGG on diabetic renal injury and the underlying mechanisms are still not yet clear. In this study, the effects of PGG on Nrf2/HO-1 and JAK2/STAT3 signaling were explored in AGE-stimulated mesangial cells. Furthermore, the Nrf2 transcriptional inhibitor ML385 was used to verify the involvement of Nrf2 in the PGG-mediated inhibition of the JAK2/STAT3 cascade. Our results showed that PGG significantly inhibited AGE-induced ROS generation and activated AGE-inhibited Nrf2/HO-1 signaling. Moreover, AGE-induced inflammatory cytokines (IL-1ß and TNF-α) and their signaling through JAK2/STAT3 were blocked by PGG. Furthermore, ML385 suppressed Nrf2/HO-1 signaling, elevated ROS and cytokine production, and activated JAK2/STAT3 cascade were reversed by PGG. These findings indicate that PGG inhibits the JAK2/STAT3 cascade by activating Nrf2/HO-1 signaling.

Fabrication of super-high transparent cellulose films with multifunctional performances via postmodification strategy.

A transparent versatile cellulose platform film was prepared from Eucalyptus pulp in this work. Based on such cellulose platform, multifunctional cellulose films with ultraviolet-shielding, photochromism, and strong mechanical strength were fabricated via nucleophilic postmodification strategy by introducing a versatile spiropyran moiety into cellulose molecules. The fabricated cellulose films exhibited super-high transmittance up to 96% and performed notable ultraviolet-shielding capacity at 200-400 nm. Moreover, the photochromic performance of cellulose films with color changes could be clearly observed by the naked eyes, and the fluorescent blue could be excited. Besides, the tensile stress of multi-functional cellulose film was about 80 MPa, which was almost 8 times stronger than that of the commercial polyethylene film at the same thickness. It is noteworthy that these superior performances promote such a cellulose platform to be a versatile precursor for fabricating various multi-functional cellulose used in the fields of out-door coating, transparent packaging, optical screen,etc.

Facile and Scalable Fabrication of Antibacterial CO2-Responsive Cotton for Ultrafast and Controllable Removal of Anionic Dyes.

A novel CO2-responsive cotton as an eco-friendly adsorbent derived from poly(4-acryloyloxybenzophenone-co-2-(dimethylamino) ethyl methacrylate) and cotton was fabricated via a facile and fast dip-coating method. As expected, upon CO2 stimulation, the protonated cotton presented CO2-induced "on-off" selective adsorption behaviors toward anionic dyes owing to electrostatic interactions. The adsorption isotherms and kinetics of the CO2-responsive cotton toward anionic dyes obeyed the Langmuir isotherm and pseudo-second-order kinetics models, respectively. It is noteworthy that the CO2-responsive cotton exhibited high adsorption capacity and ultrafast adsorption rate toward anionic dyes with the maximum adsorption capacities of 1785.71 mg g-1 for methyl orange (MO), 1108.65 mg g-1 for methyl blue (MB), and 1315.79 mg g-1 for naphthol green B (NGB), following the adsorption equilibrium times of 5 min for MO, 3 min for MB, and 4 min for NGB. Moreover, the CO2-responsive cotton also exhibited high removal efficiency toward anionic dyes in synthetic dye effluent. Additionally, the CO2-responsive cotton could be facilely regenerated via heat treatment under mild conditions and presented stable adsorption properties even after 15 cycles. Finally, the as-prepared CO2-responsive cotton exhibited outstanding antibacterial activity against E. coli and S. aureus. In summary, this novel CO2-responsive cotton can be viewed as a promising eco-friendly adsorbent material for potential scalable application in dye-contaminated wastewater remediation.

Smart composite hydrogel with pH-, ionic strength- and temperature-induced actuation.

A facile and versatile photo-patterning method to fabricate "smart" hydrogels with defined lateral and vertical inhomogeneity of hydrogel composition and dimensions has been developed via generating programmable composite hydrogels and bilayer hydrogels based on thermal and ionic strength-responsive poly(N-isopropylacrylamide) and pH-sensitive poly(acrylic acid) hydrogels. These hydrogels are capable of responding to triple-stimuli and inducing reversible "on" and "off" states upon external stimulation due to abrupt volume changes of the responsive hydrogel networks. Moreover, the composite and bilayer hydrogels show a reversible and repeatable direction-controllable bending behavior upon variation of temperature, ionic strength and pH, which is the result of the structural inhomogeneity and the modulation of the hydrogel solvation state in response to these changes. Importantly, different bending behaviors can be structurally programmed by controlling the patterned components, which undergo different swelling or shrinkage and further generate asymmetric internal stresses within the composite hydrogels in a specific manner. Additionally, such asymmetric internal stresses drive the shape deformations of the composite hydrogels, which are promising for potential applications in soft robots and actuators.

Facile Fabrication of CO2-Responsive Nanofibers from Photo-Cross-Linked Poly(pentafluorophenyl acrylate) Nanofibers.

CO2-responsive nanofibers were facilely prepared from photo-cross-linked poly(pentafluorophenyl acrylate) (PPFPA) nanofibers via "amine-active ester" chemical modification. Photo-cross-linked PPFPA nanofibers were modified with histamine under mild conditions to generate cross-linked poly(histamine acrylamide) (PHAAA) nanofibers featuring a CO2 responsiveness. As expected, the prepared cross-linked PHAAA nanofibers can exhibit a CO2-responsive behavior to induce a reversible transition from hydrophobic to hydrophilic upon alternating addition and removal of CO2 on the surface of nanofibrous membranes. Based on this finding, we could demonstrate that cross-linked PHAAA nanofibers can be employed for reversible absorption and release of protein using bovine serum albumin (BSA) as a model.

"Breathing" CO2 -, O2 -, and Light-Responsive Vesicles from a Triblock Copolymer for Rate-Tunable Controlled Release.

A well-defined amphiphilic triblock copolymer, poly[(ethylene glycol)methyl ether]-block-poly(N,N-dimethylamino ethyl methacrylate-co-2,2,2-trifluoroethyl methacrylate)-block-poly(4-(4-methoxy-phenylazo)phenoxy methacrylate) (PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA), is successfully synthesized by stepwise atom transfer radical polymerization. Owing to its amphiphilic nature, PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA can self-assemble into vesicles in aqueous solution and exhibits a reversible triple-responsive behavior toward CO2 , O2 , and light stimuli. More importantly, such vesicles can exhibit a controlled "breathing" behavior via external stimuli due to their suitable chemical structure and stimuli responsiveness. Consequently, these vesicles can be employed as nanocarriers for rate-tunable controlled release via adjustment of their membrane permeability by a single stimulus or various stimuli combinations.