Weak Acid Environment Research Articles

Construction of Intelligent Responsive Drug Delivery System and Multi-Mode Imaging Based on Gold Nanodots.

Cancer remains a formidable global problem with a high mortality rate. There are many effective anti-cancer drugs in clinical use, among which paclitaxel (PTX) has good effects on non-small cell lung cancer, ovarian cancer, and breast cancer. However, when applied to the clinic, PTX still has many limitations, such as poor water solubility, drug resistance, and side effects on healthy tissues. A gold nanodots-paclitaxel-polylysine (AuNDs-PTX-PLL) core-shell nano-system of integrated diagnosis and treatment is constructed to achieve intelligent responsive drug delivery. On the one hand, the problem of poor water-solubility and drug resistance of PTX are solved. On the other hand,the nano-system has an excellent intelligent response effect. Drugs can only be released in the weakly acidic environment of the tumor, which reduces the damage and side effects to normal tissues. Moreover, the nano-system can be used for real-time tracking and auxiliary diagnosis for the tumor through the multi-mode imaging mode, such as fluorescence, photoacoustic, and computed tomography to achieve accurate visualization. The photothermal effect of AuNDs is beneficial to promote the release of drugs. The nano-system integrates multi-mode imaging, chemotherapy, intelligent drug release in tumor weakly acidic environment, and has excellentpractical application prospects in tumor diagnosis and treatment.

Glyconanoparticles with Activatable Near-Infrared Probes for Tumor-Cell Imaging and Targeted Drug Delivery.

BackgroundMultifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery.MethodsDisulfide-functionalized dicyanomethylene-4H-pyran (DCM-SS-NH2) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation–responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π–π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs.ResultsExperimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH2 was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX.ConclusionThe fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.

A green approach to improve the yield of SAPO-34 crystal as well as its methanol-to-olefin performance

Nowadays, large amounts of aluminosilicophosphate SAPO-34 zeolite are produced in industrials annually. Here, a green strategy is developed to increase SAPO-34 crystal's yield and its catalytic performance in methanol-to-olefin (MTO) reaction. Tuning the pH value of mother liquor from alkaline to acid by rationally decreasing the environmentally unfriendly organic amine to only 57%, surprisingly the yield of SAPO-34 zeolite increases from 31% to 78%; the weak acid environment at the initial stage generates more AlPO4 precursors, which then are converted into the zeolite framework. For the first time, we found that the yield and crystallinity of the SAPO-34 crystal are positively correlated with the pH difference between gels before and after crystallization. Furthermore, the sample with the largest pH difference of about 2, showing hierarchical pore structure and mild acidity, presents excellent MTO performance: a longer lifetime of 381 ​min and a higher selectivity for ethylene plus propylene of 84.91%, compared to the conventional microporous sample of 131 ​min and 78.89%. This green approach uses less environmentally detrimental amine but enhances the yield of zeolite, in favor of the completion of the world's carbon neutrality.

Study on Mechanical Behavior and Energy Mechanism of Sandstone under Chemical Corrosion.

Chemical corrosion has a significant impact on the properties of rock materials. To study the mechanical behavior and energy mechanism of rock under chemical corrosion, this paper took the sandstone of Haitangshan tunnel in Fuxin as the research object, used a Na2SO4 solution to simulate different chemical environments, carried out a triaxial loading test on sandstone through the MTS815.02 test system, and analyzed the mechanical parameters and energy damage evolution law of sandstone under different chemical environments. The test results showed that the basic mechanical parameters (peak strength σpk, peak strain εpk, elastic modulus E, cohesion c, and internal friction angle φ) and characteristic stress parameters (closure stress σcc, initiation stress σci, and dilatancy stress σcd) of sandstone first increased and then decreased with the increase of pH in the Na2SO4 solution, Poisson’s ratio µ showed the opposite trend, and the extreme values of all parameters were taken when pH = 7. The influence degree of different pHs on the mechanical parameters of sandstone were as follows: strong acid environment (pH ≤ 4) > strong alkali environment (pH ≥ 10) > weak acid environment (4 ≤ pH < 6) > weak alkali environment (8 ≤ pH < 10) > neutral environment (6 < pH< 8). The total energy and elastic strain energy increased first and then decreased, and the dissipated energy was the opposite. The damage variable decreased first and then increased. With the increasing concentration of the Na2SO4 solution, all the above parameters changed monotonically. Based on the energy theory, the damage evolution equation considering the effect of the Na2SO4 concentration was established. Combined with the test data, the model was verified and the result was good. Under the action of Na2SO4 corrosion, Ca2+ in calcite and Fe2+ in hematite were dissolved and precipitated. With the gradual increase of Ca2+ and Fe2+ concentration, the damage variable increased gradually. The relationship between the two ion concentrations and the damage variable approximately satisfied a linear function.

Defluorination mechanism related to the activity of hydroxyl groups: A combined density functional theory calculations and experimental study

Aluminum-based (Al-based) materials are of great significance to solve the global fluoride pollution problem. Hydroxylation modification is one of the effective methods to improve the surface activity and defluorination performance of aluminum matrix materials. However, the lack of in-depth understanding of the role of hydroxyl gourp at the molecular level restricts the preparation and application of Al-based adsorbents. In this work, based on the interface of Al-based two-dimensional materials, the effects of anionic ligands, doped metals and solution H+ on the structural activity of surface hydroxyl groups were explored by DFT theoretical calculation and experimental design. Simultaneously, quantitative analysis of the contribution of each possible mechanism in the defluorination process was carried out. Both anionic exchange reaction and chemical co-adsorption determined the defluorination process. The high polarizability and more negative charge of anionic ligands was found to facilitate reducing the activity of hydroxyl groups in weak acid environment. H+ can enhance the activity of hydroxyl, and thereby strengthening the hydrogen bond (H-bond) effect, but it will have a synergistic effect with anionic ligands. Metal doping will change the electron density on O atoms, which will affect the F- adsorption effect of hydroxyl via H-bond. Compared with the existing research, we carefully studied the influence of hydroxyl group activity on the defluorination performance of aluminum matrix materials, which can provide a feasible basis for structural design of the subsequent adsorbents.

Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule

Kinesins are microtubule-based motor proteins that play important roles ranging from intracellular transport to cell division. Human Kinesin-5 (Eg5) is essential for mitotic spindle assembly during cell division. By combining molecular dynamics (MD) simulations with other multi-scale computational approaches, we systematically studied the interaction between Eg5 and the microtubule. We find the electrostatic feature on the motor domains of Eg5 provides attractive interactions to the microtubule. Additionally, the folding and binding energy analysis reveals that the Eg5 motor domain performs its functions best when in a weak acidic environment. Molecular dynamics analyses of hydrogen bonds and salt bridges demonstrate that, on the binding interfaces of Eg5 and the tubulin heterodimer, salt bridges play the most significant role in holding the complex. The salt bridge residues on the binding interface of Eg5 are mostly positive, while salt bridge residues on the binding interface of tubulin heterodimer are mostly negative. Such salt bridge residue distribution is consistent with electrostatic potential calculations. In contrast, the interface between α and β-tubulins is dominated by hydrogen bonds rather than salt bridges. Compared to the Eg5/α-tubulin interface, the Eg5/β-tubulin interface has a greater number of salt bridges and higher occupancy for salt bridges. This asymmetric salt bridge distribution may play a significant role in Eg5′s directionality. The residues involved in hydrogen bonds and salt bridges are identified in this work and may be helpful for anticancer drug design.

A pH-responsive hyaluronic acid hydrogel for regulating the inflammation and remodeling of the ECM in diabetic wounds.

Diabetes is a universal disease in the world. In the wounds of diabetic individuals, chronic inflammation and an inefficient fibrogenic process hinder the formation and deposition of the ECM, which delays the process of wound healing. To reconstruct the ECM of a diabetic patient's wound, in this work, we designed a pH-responsive "Double H-bonds" (hydrogen bond and hydrazone bond) hyaluronic acid-collagen hydrogel. This hydrogel can be self-gelled quickly in neutral and alkaline environments. But the weakly acidic inflammatory environment of diabetic wounds may accelerate the degradation of the hydrogel and the release of metformin. The in vitro results showed that the hydrogel can enhance the adhesion and infiltration of fibroblasts while inhibiting the growth of macrophages. Meanwhile, metformin could be released and polarize macrophages from M1 to M2, thereby accelerating the migration of fibroblasts and the production of collagen in a high glucose environment. The in vivo results proved that this hydrogel could remodel the ECM in diabetic mice wounds.

Hydrophobic modified poly(l‐glutamic acid) graft copolymer micelles with ultrahigh drug loading capacity for anticancer drug delivery

AbstractSelf‐assembled polymeric nanoparticle (NP) drug carriers are capable of encapsulated and controlled delivery, facilitating improvements in the therapeutic efficiency of drugs. Here we report a series of poly(l‐glutamic acid)‐g‐methoxy poly(ethylene glycol)/4‐phenylbutyl ester (PLG‐g‐mPEG/PB) copolymers, which were synthesized by esterification of 4‐phenylbutanol (PB) and PLG‐g‐mPEG in different feed ratios. The copolymers obtained form into nano‐sized micelles in aqueous solution by a self‐assembly process, with lower critical micelle concentration value for higher PB ratio in the copolymers. Variable temperature infrared spectroscopy and circular dichroism were used to prove the breaking of intermolecular hydrogen bonds after PB modification. Podophyllotoxin (PPT), an effective anticancer agent, was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interaction between the drug and the PB‐modified copolymers. Both the drug loading content and the loading efficiency increased with PB content in the PLG‐g‐mPEG/PB copolymers and reached an ultrahigh value of 28.2 wt% and 94%, respectively. The PPT‐encapsulated micelles (PPT‐NPs) were stable at pH 7.4 but dissociated and released 80% of loaded PPT in a weak acidic environment (pH 5.0). The in vitro proliferation of non‐small‐cell lung cancer cells (A549) was significantly inhibited by PPT‐NPs in a cytotoxicity assay. These results demonstrate that hydrophobic modification is an efficient route for tuning the self‐assembly behaviour and drug encapsulation of PLG‐g‐mPEG copolymers, and our PLG‐g‐mPEG/PB will serve as a promising carrier for hydrophobic anticancer drug delivery. © 2021 Society of Industrial Chemistry.

Preparation, physicochemical, and antibacterial properties of bovine serum albumin microspheres loaded with sodium nitrite

In this study, NaNO2-embedded bovine serum albumin microspheres (BSAMs) were prepared by oil-in-water emulsification method, which was covalently cross-linked with transglutaminase (TGase). Moreover, the physicochemical properties and antibacterial effect of BSAMs on Escherichia coli, Staphylococcus aureus, Pseudomonas, and beef and pork jerky were also analyzed. The particle size of BSAMs was about 0.5–2.5 μm observed by scanning electron microscopy. Almost all NaNO2 was encapsulated inside BSAMs, and there was no NaNO2 attaching on the surface of BSAMs. The encapsulation rate of NaNO2 first increased from 0 to 20 U/g TGase and then decreased from 20 to 40 U/g TGase; likewise, the release of NO first increased with the increase of TGase (0–20 U/g) and it decreased when the TGase concentration was 30 and 40 U/g. Based the results of minimal inhibitory concentration and minimal bactericidal concentration, E. coli and Pseudomonas were more sensitive to BSAMs than S. aureus. In addition, the slow release of NO from BSAMs could significantly inhibit the growth of bacteria on the surface of beef and pork jerky in a weak acidic environment compared with NaNO2 used directly, so as to achieve long-term antibacterial effect and prolong the shelf life of meat products.

Enhancing the Stability and Photothermal Conversion Efficiency of ICG by Pillar[5]arene-Based Host-Guest Interaction.

Indocyanine green (ICG) is a classical near-infrared (NIR) photothermal reagent that can be employed in clinical medical detection. Under neutral conditions, ICG can adsorb NIR light effectively for photothermal (PTT) and photodynamic (PDT) therapy. However, ICG is easily degraded in weak acid environments, which seriously restricts its application. In this work, a cationic water-soluble pillar[5]arene (WP5) was selected as the stabilizing agent for ICG. Thanks to the host-guest interaction between WP5 and alkyl sulfonate, the stability and the photothermal conversion efficiency of ICG increased remarkably upon addition of WP5 as investigated by UV-vis spectrum and photothermal studies. Furthermore, an in vitro study showed higher efficiency of WP5&ICG in killing cancer cells in a shorter treatment time than the free ICG. Hence, it is hopeful that WP5 can be a new type of supramolecular host in enhancing the stability and photothermal conversion efficiency of photosensitizers.

Styrene Maleic Acid Copolymer-Based Micellar Formation of Temoporfin (SMA@ mTHPC) Behaves as A Nanoprobe for Tumor-Targeted Photodynamic Therapy with A Superior Safety.

Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising anticancer therapeutic strategy. Previously, we developed several polymeric nanoprobes for PDT using different polymers and PDT agents. In the study, we synthesized a styrene maleic acid copolymer (SMA) micelle encapsulating temoporfin (mTHPC) that is a clinically used PDT drug, SMA@mTHPC, with a hydrodynamic size of 98 nm, which showed high water solubility. SMA@mTHPC maintained stable micelle formation in physiological aqueous solutions including serum; however, the micelles could be disrupted in the presence of detergent (e.g., Tween 20) as well as lecithin, the major component of cell membrane, suggesting micelles will be destroyed and free mTHPC will be released during intracellular uptake. SMA@mTHPC showed a pH-dependent release profile, for which a constant release of ≈20% per day was found at pH 7.4, and much more release occurred at acidic pH (e.g., 6.5, 5.5), suggesting extensive release of free mTHPC could occur in the weak acidic environment of a tumor and further during internalization into tumor cells. In vitro cytotoxicity assay showed a lower cytotoxicity of SMA@mTHPC than free mTHPC; however, similar in vivo antitumor effects were observed by both SMA@mTHPC and free THPC. More importantly, severe side effects (e.g., body weight loss, death of the mice) were found during free mTHPC treatment, whereas no apparent side effects were observed for SMA@mTHPC. The superior safety profile of SMA@mTHPC was mostly due to its micelle formation and the enhanced permeability and retention (EPR) effect-based tumor accumulation, as well as the tumor environment-responsive release properties. These findings suggested SMA@mTHPC may become a good candidate drug for targeted PDT with high safety.

Construction of photoresponsive azobenzene-decorated cationic surfactant-based self-assembled vesicles and controlled drug release

Surfactant aggregates possess a unique feature of space partitioning, and hence are widely used as drug carriers. A comprehensive understanding of the regulation of surfactant aggregation behavior can achieve the controlled release of drugs. In this work, the surface activity and photoisomerization behavior of the synthetically prepared azobenzene-functionalized cationic surfactant (AzoNC8) were thoroughly studied by analyzing the surface tension and UV-Vis absorption data, respectively. Furthermore, the self-assembling tendency of AzoNC8 with β-cyclodextrin (β-CD) was also monitored by proton nucleic magnetic resonance (1H NMR) and scanning electron microscopy (SEM). The AzoNC8 initially formed a 1:1 inclusion complex with β-CD and subsequently 2AzoNC8 @ 2β-CD self assembly unit was formed. At 10 mM concentration, the AzoNC8/β-CD self-assembled system was found to develop a vesicular structure. The photo-responsive property of AzoNC8/β-CD was further investigated using UV-Vis, 1H NMR, and transmission electron microscopy (TEM). The self-assembled system was found to exhibit a fast photo-responsive behavior under UV light and a reversible photo-response under visible light. Interestingly, the photo-induced cis-trans isomerization altered the driving force associated with the self-assembly of AzoNC8/β-CD, thereby modulating the self-assembled morphologies. In addition, an investigation with the antitumor drug of doxorubicin hydrochloride (DOX) at different pH values revealed that the self-assembly-based vesicles exhibited a quick photo-responsive drug release and a weak acid environment could improve the rate and amount of the release. Therefore, the AzoNC8/β-CD self-assembled system might be used for the controlled release of drugs and could be a promising drug carrier.

Preparation of Cu-MnOX/γ-Al2O3 by high gravity-assisted impregnation method for heterogeneous catalytic ozonation of nitrobenzene

This study considered the preparation of γ-Al2O3 supported Cu-Mn mixed oxides catalyst (Cu-MnOX/γ-Al2O3 (HGRPB)) using the high gravity-assisted impregnation method in a rotating packed bed. The catalyst had good dispersion of oxide, abundant surface oxygen vacancies, and high surface concentrations of Mn4+ and Cu0 species, which determined the excellent catalytic activity for nitrobenzene mineralization. The removal efficiency of total organic carbon by Cu-MnOX/γ-Al2O3 (HGRPB) prepared by the rotating packed bed for 45 min was almost 93.4%, which was 3 times that of single ozonation and was comparable to that of catalyst prepared by the stirred tank reactor for 6 h. Surface oxygen vacancy favored the adsorption and transformation of ozone into active species ·O2– and ·OH, which played the pivotal role in the mineralization of nitrobenzene. The lower pHPZC of Cu-MnOX/γ-Al2O3 (HGRPB), as well as the increased amount of oxygen vacancy, brought in the superior catalytic performance of Cu-MnOX/γ-Al2O3 (HGRPB) in weak acidic environment. This novel process encourages further development of high gravity towards industrial production of supported catalysts with superior catalytic ozonation performance.

Manganese carbonate nanoparticles-mediated mitochondrial dysfunction for enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) has attracted widespread attention due to its non-invasiveness and deep tissue penetration. However, the development of efficient sonodynamic nanoplatforms to improve the therapeutic efficiency is still one of the main challenges of current research. In this work, a new type of sonosensitizer prepared by a simple method, manganese carbonate nanoparticles (MnCO3 NPs), is used for enhanced SDT. MnCO3 NPs could generate large amounts of 1O2 and •OH under ultrasound irradiation. At the same time, CO2 and Mn ions could be released in a weak acid environment due to the excellent degradability of MnCO3 NPs. The CO2 bubbles caused cell necrosis by ultrasonic cavitation and used for ultrasound imaging. And Mn ions activated the mitochondrial cell apoptosis pathway. In vivo experiments proved that this sonosensitizer with mitochondrial regulatory capacity showed high tumor inhibition rates for enhanced sonodynamic tumor therapy.

PH-Responsive DNA nanoassembly for detection and combined therapy of tumor

We have developed a novel cancer theragnostic nanoassembly with high biocompatibility, stability and low toxicity which are activated rapidly by tumor microenvironment to realize selective fluorescence imaging, chemotherapy as well as chemoenzymatic therapy. The nanoprobes are synthesized by hybridization of fluorophore labeled hairpin DNAs containing a 5-aza-dC at hemimethylated CpG sites and pH-sensitive DNA sequence covalently conjugated with PEGylated GO. The aptamer, which is also covalently conjugated on PEGylated GO, enables to target the tumor site and the weak acid environment of tumor triggers the release of drug loaded by nanoprobes including functionalized DNA and DOXs, effectively activating fluorescence signals and selectively killing the tumor cells. The results revealed that the nanoprobe enables sensitive detection of pH changes within subcellular environment, selectively imaging and great synergy of multicombination therapeutic including chemotherapy and chemoenzymatic therapy, implying that developed pH activatable probe has considerable potential for diagnosis and efficient therapy of cancer.

A dual-sensitive poly(amino acid)/hollow mesoporous silica nanoparticle-based anticancer drug delivery system with a rapid charge-reversal property

The negative-to-positive surface charge-reversal capability introduced can reduce the nonspecific cellular uptake of the nanosized anticancer drug delivery systems (DDSs) and enhance the endocytosis capability by cancer cells. In this article, a novel dual-sensitive anticancer DDS with a rapid charge-reversal property was reported. Hollow mesoporous silica nanoparticle (HMSN) with a high drug loading capacity was applied as the “nanocontainer” to package the drug doxorubicin hydrochloride (DOX), then was coated by poly(aspartic acid)-graft-1-(3-aminopropyl) imidazole (PASP-g-API) through the redox-sensitive disulfide bond to obtain the DDS DOX@HMSN–SS–PASP-API. The imidazole group was not ionized at pH 7.4, resulting in a negatively charged surface of the DDS. But in the slightly acidic tumor microenvironment, the ionization of the imidazole group rapidly reversed the surface charge of the carriers for better uptake by cancer cells. After the endocytosis, the disulfide bond linking PASP-g-API and HMSN could be interrupted in the reducing environment intercellular, leading to the DOX release. The rapid charge-reversal property of the carriers was demonstrated by the in vitro studies, and the cell experiments proved that the carriers could enter the cancer cells much easier in the weakly acidic environment. Drug release studies indicated that DOX@HMSN–SS–PASP-API could release ~97% loaded DOX within 5 days with the glutathione concentration of 10 mM, demonstrating its sensitivity to redox. Also, DOX@HMSN–SS–PASP-API at pH 6.5 showed the best therapeutic effect among all the DDS groups. This dual-sensitive system with a rapid charge-reversal property should be a good complement to the researches of anticancer DDSs.

PH and H2S Dual-Responsive Magnetic Metal-Organic Frameworks for Controlling the Release of 5-Fluorouracil.

Along with the increasing cancer incidence, developing suitable drug delivery systems (DDSs) is becoming urgent to control drug release and further enhance therapeutic efficiency. Herein, a Fe-Zn bimetallic MOF-derived ferromagnetic nanomaterial was synthesized by a one-step method. The successful preparation of ferromagnetic Fe-ZIF-8 was verified by scanning electron microscopy, powder X-ray diffraction, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, and physical property measurement system characterizations. Furthermore, the release behaviors of 5-FU from the ferromagnetic carrier were investigated in a simulative cancer microenvironment of PBS buffer solution (PBS = phosphate-buffered saline, pH = 5.8) and NaHS solution. The vehicle in PBS solution of pH = 5.8 and NaHS solution of 500 μM can rapidly release 5-FU with the cumulative release percentages of 68 and 36%, respectively, within two hundred minutes. The release mechanism in the weak acid environment can be mainly attributed to the decomposition of the Fe-ZIF-8. However, the strong interaction between Zn and Fe atoms in Fe-ZIF-8 and the S atom in H2S plays an important role in the release process in the simulated H2S cancer microenvironment. The investigation of release kinetic models indicates that the 5-FU release in the PBS solutions and NaHS solution of 500 μM can be accurately fitted by a second-degree polynomial model and first-order model, respectively. In addition, the decomposition products, zinc, iron, and 2-MeIM, are endogenous and show low toxicity values [LD50 (Zn) = 0.35 g·kg-1, LD50 (Fe) = 30 g·kg-1, and LD50 (2-MeIM) = 1.4 g·kg-1]. Therefore, the low-toxicity, pH and H2S dual-stimuli-responsive, and ferromagnetic nature make the obtained Fe-ZIF-8 an ideal candidate in the field of bioactive molecule delivery.

Preparation and anti-tumor activity of PEG-PCL polymersomes loaded with curcumol derivative in HepG2 cell line

Curcumol is a natural plant product with anti-tumor properties. However, the clinical application of curcumol is limited by its low water solubility. In this study, we synthesized a curcumol derivative 2e (CD-2e) with improved bioavailability and evaluated its cell growth-regulating activities in human hepatoma HepG2 cells, a liver cancer precursor cell line. Using the clone formation assay, we detected that CD-2e inhibits proliferation and activity of HepG2 cells more effectively than curcumol. Flow cytometry analysis indicated that CD-2e can induce HepG2 cell apoptosis and arrests cell cycle in S phase. Acridine orange-ethidium bromide(AO-EB) double staining indicated that CD-2e triggers HepG2 cell apoptosis in a time-dependent manner. Additionally protein expression analysis showed that CD-2e treatment reduced expression levels of c-Jun N-terminal kinase 1 (JNK1) and its phosphorylated form, P-JNK1. PEG-PCL polymersome carrying CD-2e (PEG-PCL-CD-2e) were generated to improve drug delivery. The prepared PEG-PCL-CD-2e had a uniform particle size distribution, with an average particle size of about 190 nm, and good in vitro stability. The drug release and cell uptake experiments showed that PEG-PCL-CD-2e can rapidly release CD-2e in a weak-acid environment in vitro. Pharmacokinetic studies indicated that, compared with free CD-2e, PEG-PCL-CD-2e enhanced Cmax and Area Under Curve (AUC) (0-∞) by about 1.93-fold and 2.45-fold. The T1/2 was prolonged to 2.59 ± 0.03 h.

Solar irradiation induced oxidation and adsorption of arsenite on natural pyrite

The migration and bioavailability of toxic elemental arsenic (As) are influenced by the adsorption and redox processes of sulfide minerals in waters around mining areas. Pyrite is the most abundant sulfide mineral in the Earth's crust and exhibits certain photochemical activity. However, the adsorption and redox behaviors of arsenite (As(III)) on pyrite surface under solar irradiation remain unclear. Here, the interaction between As(III) and natural pyrite was investigated under light irradiation. The results indicated that solar irradiation promotes As(III) oxidation and adsorption on pyrite surface due to reactive oxygen species (ROS) intermediates. The reactions between H2O/O2 and hole–electron pairs (hvb+–ecb−) on excited pyrite and the oxidation of Fe2+ released from pyrite by dissolved O2 contributed much to the generation of OH•, O2•− and H2O2 under light irradiation. ROS production and As(III) oxidation were accelerated by dissolved O2. An increase in pH within 5.0 to 9.0 decreased the concentration of OH• but increased that of H2O2 and the amount of oxidized As(III). In weakly acidic and neutral environments, OH• was mainly responsible for As(III) oxidation, while H2O2 contributed much to As(III) oxidation in weakly alkaline environments. Partial arsenate (As(V)) was adsorbed on pyrite and newly formed ferrihydrite. The present work enriches the understanding of As migration and transformation in the waters around mining areas, and provides a potential method for As(III) removal by using pyrite under solar irradiation.

Preparation of hydrophobically modified carboxylated pullulan nanoparticles for evaluating the effect of hydrophobic substitution on the properties and functions of nanoparticles

ABSTRACT We designed three cholesterol-modified carboxylated pullulan (CHSP) polymers modified with different degrees of substitution (DS). Nuclear magnetic resonance (NMR) was used to characterize CHSP polymer and calculate the DS, which were 2.12%, 4.36% and 6.05% for CHSP1, CHSP2 and CHSP3. The particle sizes identified by dynamic light scattering (DLS) were approximately 229.4 nm, 185.1 nm and 178.0 nm.The mitoxantrone (MTO) loadings of three nanoparticles were 5.28%, 6.71% and 7.68%. At pH 6.8, 72 hours later, the drug release rates were 95.42%, 86.88%, and 80.16%. In the weakly acidic environment, the drug release rate was significantly accelerated but still showed three types of nanoparticles and hydrophobic substitution degree-related slow release characteristics. In the cytotoxicity experiments, it was found that the inhibitory effect of the three nanoparticles on hepatoma cells is related to the degree of hydrophobic substitution, and the nanoparticles with the lowest hydrophobic substitution degree have the strongest inhibitory effect.