Computer-Aided Molecular Design of Ionic Liquids as Advanced Process Media: A Review from Fundamentals to Applications.

The unique physicochemical properties, flexible structural tunability, and giant chemical space of ionic liquids (ILs) provide them a great opportunity to match different target properties to work as advanced process media. The crux of the matter is how to efficiently and reliably tailor suitable ILs toward a specific application. In this regard, the computer-aided molecular design (CAMD) approach has been widely adapted to cover this family of high-profile chemicals, that is, to perform computer-aided IL design (CAILD). This review discusses the past developments that have contributed to the state-of-the-art of CAILD and provides a perspective about how future works could pursue the acceleration of the practical application of ILs. In a broad context of CAILD, key aspects related to the forward structure-property modeling and reverse molecular design of ILs are overviewed. For the former forward task, diverse IL molecular representations, modeling algorithms, as well as representative models on physical properties, thermodynamic properties, among others of ILs are introduced. For the latter reverse task, representative works formulating different molecular design scenarios are summarized. Beyond the substantial progress made, some future perspectives to move CAILD a step forward are finally provided.

Dihydroxyl-Cooperative 1,2,4-Triazole-Based Ionic Liquid for Robust Reversible CO2 Absorption.

The development of aqueous absorbents for CO2 capture is significantly important to reduce global industrial gas emissions through high regeneration efficiency and low energy consumption. Herein, we newly designed and prepared a dihydroxylated ionic liquid (IL) bis(2-hydroxyethyl)dimethylammonium 1,2,4-triazole ([N1,1,2OH,2OH][TZ]) for highly efficient CO2 absorption through anion-cation cooperative interactions. A superior capacity of 1.33 mol of CO2 per mol of IL and excellent reversibility have been achieved by the introduction of dihydroxy sites on the ammonium-based Tz IL. 1H and 13C nuclear magnetic resonance, Fourier transform infrared, and quantum chemical calculations demonstrate bihydroxyl-cooperative absorption of CO2 via hydrogen bond interaction between the cation and anion of the IL. The theory calculation shows that IL displays a superlow reactive absorption enthalpy, favorable to the reversible CO2 absorption, which can maintain an initial absorption capacity of 98.5% with the cycle numbers of 100, implying the facile regeneration and superlow energy consumption. Thus, the functionalized ILs toward group cooperative gas absorption and excellent reversibility may open a door to designing new materials for enhancing CO2 absorption and utilization.

Design, Synthesis, and Biological Evaluation of New Urushiol Derivatives as Potent Class I Histone Deacetylase Inhibitors.

In the present study, a novel series of 11 urushiol-based hydroxamic acid histone deacetylase (HDAC) inhibitors was designed, synthesized, and biologically evaluated. Compounds 1-11 exhibited good to excellent inhibitory activities against HDAC1/2/3 (IC50 : 42.09-240.17 nM) and HDAC8 (IC50 : 16.11-41.15 nM) in vitro, with negligible activity against HDAC6 (>1409.59 nM). Considering HDAC8, docking experiments revealed some important features contributing to inhibitory activity. According to Western blot analysis, select compounds could notably enhance the acetylation of histone H3 and SMC3 but not-tubulin, indicating their privileged structure is appropriate for targeting class I HDACs. Furthermore, antiproliferation assays revealed that six compounds exerted greater in vitro antiproliferative activity against four human cancer cell lines (A2780, HT-29, MDA-MB-231, and HepG2, with IC50 values ranging from 2.31-5.13 µM) than suberoylanilide hydroxamic acid; administration of these compounds induced marked apoptosis in MDA-MB-231 cells, with cell cycle arrest in the G2/M phase. Collectively, specific synthesized compounds could be further optimized and biologically explored as antitumor agents.

Clinical and pathological features of omicron variant of SARS-CoV-2-associated kidney injury.

Kidney injury is common in patients with Coronavirus Disease-19 (COVID-19), which is related to poor prognosis. We aim to summarize the clinical features, athological types, and prognosis of COVID-19 associated kidney injury caused by the Omicron strain. In this study, 46 patients with Omicron-associated kidney injury were included, 38 of whom performed renal biopsy. Patients were divided into two groups: group A for patients with onset of kidney injury after SARS-CoV-2 infection; group B for patients with pre-existing kidney disease who experienced aggravation of renal insufficiency after SARS-CoV-2 infection. The clinical, pathological, and prognostic characteristics of the patients were observed. Acute kidney injury (AKI) (35%) was the most common clinical manifestation in group A. Patients in group B mainly presented with chronic kidney disease (CKD) (55%) and nephrotic syndrome (NS) (40%). The pathological type was mainly IgA nephropathy (IgAN) (39% in group A and 45% in group B). Among all of them, one case presenting with thrombotic microangiopathy had worse kidney function at biopsy time. Mean serum C3 levels were 1.2 ± 0.5 and 1.0 ± 0.2 g/L in group A and group B, respectively. In renal tissues, C3 deposits were observed in 71.1% of patients. 11.8% (n = 2) patients experienced deterioration of renal function after treatment, but no patients developed to end-stage renal disease. In our single-center study in China, the main clinical manifestations were AKI, CKD, and NS, while the main pathological type was IgAN. Compared with previous strains of SARS-CoV-2, patients with the Omicron infection had a favorable prognosis.

Boosting Hydrogen Peroxide Electrosynthesis via Modulating the Interfacial Hydrogen-Bond Environment.

Designing highly efficient and stable electrode-electrolyte interface for hydrogen peroxide (H2 O2 ) electrosynthesis remains challenging. Inhibiting the competitive side reaction, 4 e- oxygen reduction to H2 O, is essential for highly selective H2 O2 electrosynthesis. Instead of hindering excessive hydrogenation of H2 O2 via catalyst modification, we discover that adding a hydrogen-bond acceptor, dimethyl sulfoxide (DMSO), to the KOH electrolyte enables simultaneous improvement of the selectivity and activity of H2 O2 electrosynthesis. Spectral characterization and molecular simulation confirm that the formation of hydrogen bonds between DMSO and water molecules at the electrode-electrolyte interface can reduce the activity of water dissociation into active H* species. The suitable H* supply environment hinders excessive hydrogenation of the oxygen reduction reaction (ORR), thus improving the selectivity of 2 e- ORR and achieving over 90 % selectivity of H2 O2 . This work highlights the importance of regulating the interfacial hydrogen-bond environment by organic molecules as a means of boosting electrochemical performance in aqueous electrosynthesis and beyond.

Fast Assembly of Metal Organic Framework UiO-66 in Acid-Base Tunable Deep Eutectic Solvent for the Acetalization of Benzaldehyde and Methanol.

Zirconium-based metal-organic frameworks (MOFs) have attracted extensive attention owing to their robust stability and facile functionalization. However, they are generally prepared in common volatile solvents within a long reaction time. Here, we introduced environmentally friendly, cheap, and acid-based tunable deep eutectic solvents (DESs) formed from 2-methyl imidazole (MIm) and p-toluenesulfonic acid (PTSA) which significantly accelerated the assembly of zirconium-based MOF (UiO-66) without any aggressive additives. PTSA in acidic DES and ZrOCl2 preliminarily formed Zr(IV) oxo organic acid framework, whereas basic DES completely dissolved the ligand of UiO-66. The strong hydrogen bond effect of PTSA and MIm efficiently accelerated the linker exchange between zirconium oxo organic coordination in acidic DES and benzenedicarboxylate linker in weak basic DES within a reaction time of 2 h at 50 °C. Thus, UiO-66 was quickly assembled with small particle sizes and used as an excellent catalyst for the acetalization of benzaldehyde and methanol. Therefore, the developed synthesis approach provides a new green strategy to quickly prepare and design various structures of metal-based compounds under mild reaction conditions.

Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein.

Ursolic acid (UA) is an accessible triterpenoid, widely applied in the design and synthesis of antitumor compounds. However, the mechanism of its anti-tumor effect is still unclear. To verify the molecular mechanism of its biological activity, based on the bifunctional activity of ubiquitination and subsequent proteasomal degradation of the target protein of the proteolysis-targeting chimeras (PROTACs) strategy, here we report the design, synthesis and cellular activity of six UA PROTAC hydrochloride compounds 1A-1F, in which UA acts as the binding ligand of the PROTAC and is linked to thalidomide (E3 ligand) through a series of synthetic linkers. The results revealed that compound 1B, connected with a POE-3 (3-Polyoxyether) possessed remarkable in vitro antitumor activity (with the IC50 value of 0.23 ~ 0.39 µM against A549, Huh7, HepG2). WB results demonstrated that the administration of compound 1B induced significant degradation of MDM2 (only 25% to that of SM1), and promoted the expression of P21 and PUMA proteins, and thus inhibited the proliferation (77.67% of 1B vs 60.37% of CON in G1 phase) and promoted the apoptosis (26.74% of 1B vs 3.35% of CON) of A549 cells. This work demonstrated proof of designing the efficient target protein degradation by UA PROTACs with the POE linkers. In addition, we confirmed that UA possess the characteristic of targeted-binding the protein of murine double minute-2 protein (MDM2). This will lay a foundation for the comprehensive utilization of forest natural compound UA.

Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study.

A series of novel C15 urushiol derivatives were designed by introducing a pechmann structure and F-, Cl-, and Br-nitro substituents with different electronic properties into its alkyl side chain, as well as a triazolyl functional group in its aromatic oxide. Their chemical structures were determined based on the analysis of the NMR (nuclear magnetic resonance) spectroscopic and mass spectrometric data. The results showed that compound 4 exhibited a strong inhibition of the HepG2 cell proliferation (half maximal inhibitory concentration (IC50): 2.833 µM to human hepatocellular carcinoma (HepG2), and 80.905 µM to human normal hepatocytes (LO2)). Furthermore, it had an excellent synergistic effect with levopimaric acid. The nitrogen atom of the triazole ring formed a hydrogen-bonding interaction with Gly103, Gly154, and Tyr308, which made compound 4 bind to histone deacetylase (HDAC)2 more tightly. One triazole ring and His33 formed a π⁻π stacking effect; the other, whose branches were deep into the pocket, further enhanced the interaction with HDAC2. Meanwhile, compound 4 involved a hydrophobic interaction with the residues Phe210 and Leu276. The hydrophobic interaction and π⁻π stacking provided powerful van der Waals forces for the compounds.

Synthesis and Evaluation of C15 Triene Urushiol Derivatives as Potential Anticancer Agents and HDAC2 Inhibitor.

A series of C15 triene urushiol derivatives were synthesized and evaluated for their anti-HepG2 aggregation in vitro. The results indicated that all compounds had an effective anti-HepG2 vitality. Compound 1 was a potent inhibitor of HepG2 with IC50 of 7.886 µM and 150 µM against LO2. Moreover, compound 1 increased the apoptosis of HepG2. Compound 1's thiol sulfur formed hydrogen bonding interactions with Gly154 and Tyr308, respectively, and made it bound more closely to HDAC2. In addition, it also formed hydrophobic interactions with the residues His33, Pro106, Val107, Gly154, Phe155, and His183, and was provided with a strong van der Waals force by the hydrophobic action.

Urushiol oligomer preparation and evaluations of their antibacterial, antioxidant, and thermal stability.

There have been studies published on the composition and coating uses of raw lacquers following enzymatic oxidative polymerization. The change of urushiol' thermal stability and biological activity following polymerization to create oligomer, however, has received little attention. This work using silica gel column chromatography to separate urushiol and urushiol oligomer from polymerized raw lacquer and assessed its antibacterial, antioxidant, and thermal stability in an effort to decrease the allergenicity of urushiol and increase its application. By using gel chromatography, the urushiol oligomer were discovered to be polymers with 2-5 degrees of polymerization. According to characterization results from techniques like UV, FT-IR, and 1H NMR, urushiol was converted into urushiol oligomer by addition reactions, and C-C coupling. The findings demonstrated that the urushiol oligomer' IC50 values for scavenging DPPH and ABTS free radicals were 40.8 and 27.4 µg/mL, respectively, and that their minimum inhibitory concentrations against Staphylococcus aureus and Staphylococcus epidermidis were 250 and 125 µg/mL. The urushiol oligomer's thermogravimetric differential curve peak temperature (461.8 °C) was higher than urushiol's (239.5 °C), indicating that urushiol undergoes polymerization with enhanced thermal stability. The study's findings establish a foundation for the use of polymerized urushiol and urushiol oligomer in applications including functional materials and additives.

Advances in Separation, Biological Properties, and Structure-Activity Relationship of Triterpenoids Derived from Camellia oleifera Abel.

Extensive research has been conducted on Camellia oleifera Abel., a cultivar predominantly distributed in China, to investigate its phytochemical composition, owning to its potential as an edible oil crop. Pentacyclic triterpene saponins, as essential active constituents, play a significant role in contributing to the pharmacological effects of this cultivar. The saponins derived from C. oleifera (CoS) offer a diverse array of bioactivity benefits, including antineoplastic/bactericidal/inflammatory properties, cardiovascular protection, neuroprotection, as well as hypoglycemic and hypolipidemic effects. This review presents a comprehensive analysis of the isolation and pharmacological properties of CoS. Specially, we attempt to reveal the antitumor structure-activity relationship (SAR) of CoS-derived triterpenoids. The active substitution sites of CoS, namely, C-3, C-15, C-16, C-21, C-22, C-23, and C-28 pentacyclic triterpenoids, make it a unique and highly valuable substance with significant medicinal and culinary applications. As such, CoS can play a critical role in transforming people's lives, providing unique medicinal benefits, and contributing to the advancement of both medicine and cuisine.

Vortex-blending matrix solid-phase dispersion and UPLC-Q-TOF/MS were proposed to extract and examine the urushiols from Toxicodendron vernicifluum bark.

Toxicodendron vernicifluum bark has been used for many years as a component in foods and as a traditional herbal medication. Unfortunately, the presence of urushiols, which induce allergies, limits its application. This study used a vortex-blending matrix solid-phase dispersion microextraction technique to extract urushiols from Toxicodendron vernicifluum bark. HPLC was used to evaluate the amounts of the extracted urushiols (15:0, 15:1, 15:2, and 15:3). The modified magnetic adsorbent was prepared through an in situ coprecipitation method and characterized using a variety of techniques. The optimized extraction conditions are as follows: using magnetic Zeolite Socony Mobil-Five as an adsorbent, a 1:2 sample/adsorbent ratio, 2.5 min of vortex-blending time, 4 mL of 0.1% (V/V) trifluoroacetic acid-methanol as the elution solvent and 8 min of ultrasound time. There was good linearity and high repeatability in the method. Furthermore, the limits of detection for the urushiols ranged from 0.20 to 0.50 µg/mL. Under the optimized conditions, 50 compounds were identified by ultra high performance liquid chromatography and quadrupole time-of-flight mass spectrometry. These compounds included 8 phenolic acids, 9 monomeric urushiols, 11 urushiol dimers, 10 other components, and 11 flavonoids. The suggested approach, which has the advantages of few stages and high extraction efficiency over existing extraction procedures, is a potentially useful method for obtaining and evaluating urushiols in raw materials or extracts.

Bioactive chitosan-citral Schiff base zinc complex: A pH-responsive platform for potential therapeutic applications.

The application of CO2 supercritical fluid (SCF) technology has developed rapidly because of its non-toxic, environmentally friendly, mild reaction conditions and safety. The SCF technology can effectively speed up the reaction process of nano-material synthesis, and maintains a high degree of controllability and repeatability. This study mainly included carboxymethyl chitosan sodium salt (CCS), citral (CT), p-coumaric acid (CA), and ZnSO4 as raw materials to prepare CCS-CT-CA-Zn complex as a pH-responsive agent and was investigated using supercritical fluid technique. The coordination structure of Bridge-CCS-CT-CH3COO-CA-Zn-Schiff base/OH and the morphology of the complex agents were verified. The prepared CCS-CT-CA-Zn complex showed good dispersion and uniformity (mean size: 852 ± 202 nm, PdI: 0.301, and mean zeta potential: -31 ± 6 mV). Also, it has a good pH responsive release in an acid environment. Besides, both of CCS-CT-CA-Zn complex (DS-B) and its decomposed mixture in acid (DS-A) demonstrated significant antioxidant and anti-vibrio activity. Moreover, both DS-B complex and DS-A mixture inhibited biofilm formation, swimming, and swarming motilities of V. parahaemolyticus in a dose-dependent manner. This work will provide a scientific basis for the further design and development of natural products derived antibacterial-antioxidant complex agents, food additives and feed additives.

Spontaneous Combustion Characteristics of Activated Carbon Modified via Liquid Phase Impregnation during Drying.

Spontaneous combustion characteristics are important issues for the safe operation of the wet-modified activated carbon drying process. The spontaneous combustion characteristics of activated carbon modified via liquid phase impregnation were fully investigated in this study. The modified activated carbon was prepared using columnar activated carbon and 4-amino-1,2-butanediol solution. Physical properties and surface functional group analyses were performed for activated carbon before and after modification. The ignition temperature of activated carbon before and after modification was then characterized using the methods of GB/T20450-2006, thermogravimetry-derivative thermogravimetry (TG-DTG), and TG-mass spectrometry (TG-MS). At the same time, the activation energy of activated carbon before and after modification was calculated by using thermodynamic analysis. Furthermore, a new self-designed test platform was introduced to investigate the spontaneous combustion characteristics of wet-modified activated carbon under the drying temperatures of 150, 175, 180, and 210 °C. The results show that the specific surface area of Brunauer, Emmett, and Teller (BET) is decreased by 368 m2·g-1, the total volume of pore size is decreased by 0.17 cm3·g-1, and the content of oxygen-containing functional groups is decreased by 0.071 mmol/g compared with row activated carbon. The ignition temperatures of the sample before modification characterized by the three methods are 483, 596, and 599 °C, respectively. The ignition temperatures of the sample after modification are 489, 607, and 611 °C, respectively. The activation energy of the modified activated carbon is increased by 35 kJ/mol compared to the original activated carbon. It is concluded that the temperature that triggers the modified activated carbon combustion during the drying process is between 175 and 180 °C, and the heat is mainly gathered at the longitudinal center of the combustion chamber through the investigation of spontaneous combustion experiments. The results in this study can contribute to safe production to prevent combustion in the process of modifying activated carbon during the drying process.

Cationic and anionic defect decoration of CoO through Cu dopants and oxygen vacancy for a High­Performance supercapacitor.

CoO has attracted increasing attention as an electrochemical energy storage owing to its excellent redox activity and high theoretical specific capacitance. However, its low inherent electrical conductivity results in sluggish reaction kinetics, and the poor rate capability of CoO limits its widespread applications. Herein, a multiple-defect strategy of engineering oxygen vacancies and Cu-ion dopants into the low-crystalline CoO nanowires (Ov-Cu-CoO) is successfully applied. Because of the advantage of the dual defect synergetic effect, the electronic structure and charge distribution are effectively modulated, thus enhancing the electrical conductivity and enriched redox chemistry. The obtained Ov-Cu-CoO electrode exhibits a high specific capacity of 1388.6 F⋅g-1 at a current density of 1 A⋅g-1, an ultrahigh rate performance (81.2% of the capacitance retained at 20 A⋅g-1) and excellent cycling stability (101.1% after 10,000 cycles). Moreover, an asymmetric supercapacitor device with Ov-Cu-CoO as the positive electrode having a high energy density of 44.1 W⋅h⋅kg-1 at a power density of 800 W⋅kg-1, and can still remain 27.2 W⋅h⋅kg-1 at a power density of 16 kW⋅kg-1. This study demonstrates an effective strategy to enhance electrochemical performance of CoO that can be easy applied to other transition metal oxides.

Developing fisetin-AgNPs incorporated in reinforced chitosan/pullulan composite-film and its application of postharvest storage in litchi fruit.

In this study, Toxicodendron vernicifluum fisetin chelated silver nanoparticles (FT-AgNPs) with outstanding antioxidant and antimicrobial activities were constructed via self-assembly. To surprise, 0.6 wt% FT-AgNPs was compatibly dispersed into the 1:1 chitosan/pullulan (CS/PUL, CP) matrix. The hydrogen bonding and electrostatic interaction between FT-AgNPs and CP, slightly increased the CP thermal stability, and greatly enhanced the tensile strength to 61.2 MPa, water vapor permeability below 20 kg/m2•d. Furthermore, after treated with the composite hydrocolloid film (FT-AgNPs/CP), the reactive oxygen species level of the treated Aspergillus niger cells was significantly increased, and the membrane permeability was enhanced. It effectively slowed down the decay of litchi fruit induced by microbial infection under the storage at 25 °C (15 d of the 0.6 % FT-AgNPs/CP treatment vs 9 d of the control). In addition, 0.024 µg/kg Ag+ residual in lichi pulp verified the qualified safety of the application of the 0.6 % FT-AgNPs/CP.

Advances of Ionic Liquids and Deep Eutectic Solvents in Green Processes of Biomass-Derived 5-Hydroxymethylfurfural.

5-Hydroxymethylfurfural (HMF) is identified as an important bio-based platform chemical to bridge petroleum-based and biomass-based resources. It can be obtained through dehydration of various carbohydrates as well as converted to value-added fuels and chemicals. As designer solvents, ionic liquids (ILs) and deep eutectic solvents (DESs) have been widely used in catalytic transformation of biomass derivatives to various chemicals. This Review summarizes recent progress in experimental and theoretical studies on dehydration of carbohydrates such as fructose, glucose, sucrose, cellobiose, chitosan, cellulose, inulin, and even raw biomass to generate HMF using ILs and DESs as catalysts/cocatalysts and/or solvents/cosolvents. It also gives an overview of IL and DES-involved catalytic transformation of HMF to downstream products via oxidation, reduction, esterification, decarboxylation, and so forth. Challenges and prospects of ILs and DESs are also proposed for further production of HMF and HMF derivatives from biomass in green and sustainable processes.

Quantitative assessment of the contribution of soil organic matter functional groups and heteroatoms to PAHs adsorption based on the COSMO-RS model.

Soil organic matter (SOM) is considered as a pivotal factor influencing the adsorption of pollutants. However, few prior quantitative investigations of the SOM functional group distribution to the contaminants' fate have been conducted. In this paper, the SOM cluster method based on COSMO-RS theory has been conducted to illustrate the chemical composition variables of SOM that affect the polycyclic aromatic hydrocarbons (PAHs) fate in quantitative terms. In the theoretical simulations, the contributions of carbonyl, carboxyl, aromatic, oxyalkyl and aliphatic groups in SOM to phenanthrene (Phe) and pyrene (Pyr) adsorption are evaluated by calculating the partition coefficients (LogP). The results show that the increase in oxyalkyl content leads to a decrease in LogP. Inversely, carbonyl and carboxyl groups of SOMs positively associated with Phe adsorption. The changes in aromatic and alkyl components have a similar magnitude of influence on LogP. Moreover, the effect of non-carbon-based functional groups in SOM on the Phe partitioning has been examined for the first time. The increase of sulfur and nitrogen content in SOM hinder Phe adsorption, while the rise of phosphorus content promotes the adsorption. In soil adsorption experiments, four natural soils, characterized by X-ray photoelectron spectroscopy (XPS) and Diffuse reflectance infrared Fourier transform (DRIFT), are selected to verify the influence of SOM functional group distribution. Comparing the experimental SOM-water partition coefficient (LogKoc) with the simulation predicted LogP suggests that the COSMO-RS based SOM cluster method can predict PAHs adsorption ability in SOM.

The aqueous assembly preparation of OPs-AgNPs with phenols from olive mill wastewater and its mechanism on antimicrobial function study.

To valorise olive mill wastewater phenols (OPs) potentially applied in food preservation, a novel stable and regularly spherical OPs-AgNPs (Davg = 78 nm) were successfully assembled in aqueous solution under the optimized conditions (pH 8.0, 5 mM AgNO3, 35C and 30 min). The results of antimicrobial zone diameters indicated that 50 µg/mL of promising OPs-AgNPs presented excellent antimicrobial effects. Especially, the cell wall damages of E. coli ATCC 23,815 were caused when OPs-AgNPs concentration was exceeded its MIC (8.58 µg/mL). Also, a significant down-regulating of the Ca2+-ATPase activity in E. coli was revealed, and the intracellular Ca2+ concentrations were thus decreased from 12.5 to 1.35 µg/mL after a treatment for 3 h. The apoptosis level of E. coli was significantly increased more than the control (55.13% of OPs-AgNPs vs 9.90% of control). In sum, OPs exerts enhanced antimicrobial function via penetrating cell membrane and targeting Ca2+-ATPase after chelated with AgNPs.

Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity.

PURPOSE: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(ß-amino ester) (mPEG-PBAE). MATERIALS AND METHODS: We synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo. RESULTS: The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation. CONCLUSION: The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.