Delivery of Doxorubicin by Ferric Ion-Modified Mesoporous Polydopamine Nanoparticles and Anticancer Activity against HCT-116 Cells In Vitro.

In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer.

A Tiered Ecological Risk Assessment of Caffeine by Using Species Sensitivity Distribution Method in the Nansi Lake Basin.

Caffeine has been reported toxic to aquatic organisms, and it frequently occurs at relatively high concentrations in most of surface waters. However, it is difficult to control caffeine pollution because of the lack of Water Quality Criteria (WQC). In this study, species sensitivity distribution method and Log-normal model were applied to derive caffeine WQC as 83.7 ng/L. Meanwhile, concentrations of caffeine in the Nansi Lake basin were detected in 29 sampling sites, with the mean of 99.3 ng/L. The levels of caffeine in tributaries were higher than those in the lakes. In addition, a tied ecological risk assessment method was applied to assess the adverse effect of caffeine on aquatic system. The joint probability curve indicated that ecological risk might exist 3.1% of surface water in the study area, while 5% threshold (HC5) was set up to protect aquatic species. Generally, caffeine posted a low risk to aquatic organisms in the Nansi Lake basin.

In vitro Antitumor Properties of Fucoidan-Coated, Doxorubicin-Loaded, Mesoporous Polydopamine Nanoparticles.

Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.

Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa.

PURPOSE: This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS: Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated. RESULTS: The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies. CONCLUSIONS: Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.

Characterization and abolishment of the cyclopiazonic acids produced by Aspergillus oryzae HMP-F28.

Extracellular alkalinization and H2O2 production are important early events during induced resistance establishment in plants. In a screen for metabolites as plant resistance activators from 98 fungal isolates associated with marine sponge Hymeniacidon perleve, the cyclopiazonic acids (CPAs) produced by Aspergillus oryzae HMP-F28 induced significant extracellular alkalinization coupled with augmented H2O2 production in tobacco cell suspensions. Bioassay-guided fractionation led to the isolation and structural elucidation of a new CPA congener (4, 3-hydroxysperadine A) and three known ones (1-3). To construct a mutasynthetic strain to generate unnatural CPA analogues, a hybrid pks-nrps gene (cpaS) was disrupted to abolish the production of the critical precursor of cyclo-acetoacetyl-L-tryptophan (cAATrp) and all the downstream CPA products. Elimination of cAATrp will allow cAATrp mimics being processed by the CPA biosynthetic machinery to produce CPA derivatives with designed structural features.

Nine new diterpenes from the leaves of plantation-grown Cunninghamia lanceolata.

Nine new diterpenes named lanceolatanol hydroperoxide (1), epilanceolatanol hydroperoxide (2), lanceolatanoic acid hydroperoxide (3), epilanceolatanoic acid hydroperoxide (4), lanceolatanol (5), lanceolatanoic acid (6), 11-acetoxylanceolatanoic acid (7), 11-acetoxylanceolatanoic acid methyl ester (8) and epoxyhinokiol (13) were characterized from the leaves of plantation-grown Cunninghamia lanceolata along with twelve known compounds. The compounds were evaluated for their growth inhibitory activities against the human prostate cell line (PC-3).

Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly.

Cyclic dipeptides produced by fungus Eupenicillium brefeldianum HMP-F96 induced extracellular alkalinization and H2O 2 production in tobacco cell suspensions.

Extracellular alkalinization and H2O2 production are important early events during induced systemic resistance (ISR) establishment in plants. In a screen for metabolites as potential ISR activators from 98 fungal isolates associated with marine sponge Hymeniacidon perleve, the crude metabolites of fungus Eupenicillium brefeldianum HMP-F96 induced significant extracellular alkalinization coupled with H2O2 production in tobacco cell suspensions. A combined bioactivity and (1)H NMR-guided fractionation approach was used to disclose the chemical determinants responsible for the activities. Eight cyclic dipeptides were purified from the fermentation broth of the strain and were structurally characterized by NMR and MS experiments. This study represents the first report of the occurrence of cyclic dipeptides in E. brefeldianum and of their activities of inducing extracellular alkalinization and H2O2 production in tobacco cell suspensions.

Polydopamine-Modified Copper Coordination Mesoporous Silica Nanoparticles Loaded with Disulfiram for Synergistic Chemo-Photothermal Therapy.

Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.

pH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy.

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.

In situ generation of copper(â ¡)/diethyldithiocarbamate complex through tannic acid/copper(â ¡) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.

Dextran-Based Antibacterial Hydrogel Dressings for Accelerating Infected Wound Healing by Reducing Inflammation Levels.

Infected wounds pose challenges such as exudate management, bacterial infections, and persistent inflammation, making them a significant challenge for modern dressings. To address these issues in infected wounds more effectively, aerogel-hydrogel biphase gels based on dextran are developed. The gel introduced in this study exhibits antibacterial and anti-inflammatory properties in the process of wound therapy, contributing to accelerated wound healing. The aerogel phase exhibits exceptional water-absorption capabilities, rapidly soaking up exudate from infected wound, thereby fostering a clean and hygienic wound healing microenvironment. Concurrently, the aerogel phase is enriched with hydrogen sulfide donors. Following water absorption and the formation of the hydrogel phase, it enables the sustained release of hydrogen sulfide around the wound sites. The experiments confirm that hydrogen sulfide, by promoting M2 macrophage differentiation and reducing the levels of inflammatory factors, effectively diminishes local inflammation levels at the wound site. Furthermore, the sodium copper chlorophyllin component within the hydrogel phase demonstrates effective antibacterial properties through photodynamic antimicrobial therapy, providing a viable solution to wound infection challenges.

A quaternized chitosan and carboxylated cellulose nanofiber-based sponge with a microchannel structure for rapid hemostasis and wound healing.

A hemostatic sponge should perform rapid hemostasis and exhibit antibacterial properties, whilst being non-toxic, breathable, and degradable. This study prepared a hemostatic sponge (CQTC) with microchannels, specifically a microchannel structure based on quaternized chitosan (QCS) and carboxylated cellulose nanofibers (CCNF) obtained by using tannic acid and Cu2+ complex (crosslinking agent). The sponge had low density and high porosity, while being degradable. The combination of microchannels and three-dimensional porous structure of CQTC leads to excellent liquid absorption and hemostasis ability, based on a liquid absorption rate test and in vitro hemostasis experiment. In addition, CQTC exhibited excellent antibacterial activity against both gram-negative and gram-positive bacteria, and it promoted wound healing. In conclusion, this porous and microchannel hemostatic sponge has broad application prospects as a clinical wound hemostatic material.

Chitosan-based carbon nitride-polydopamine­silver composite dressing with antibacterial properties for wound healing.

Infection represents a major clinical barrier that delays wound healing, while the overuse of antibiotics can lead to bacterial resistance. Hence, it is of particular important to develop a new type of dressing to combat bacterial resistance. Herein, a carbon nitride-polydopamine­silver complex (C3N4-PDA-Ag) was prepared using the photocatalyst C3N4 and silver nanoparticles (Ag NPs) to achieve a synergistic antimicrobial effect. The solution casting method was then employed to further modify the C3N4-PDA-Ag complex by compounding it with chitosan (CS), thereby forming a C3N4-PDA-Ag@CS film. The results revealed that the C3N4-PDA-Ag@CS film exhibits superior antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa compared to the CS group. The hemolysis, cytotoxicity, and in vivo implantation experiments indicated that the composite film possesses excellent in vitro and in vivo biocompatibility. In addition, the composite dressing promoted wound healing in infected mice by facilitating collagen deposition and accelerating epidermal regeneration. Collectively, the findings of this study clearly demonstrate that the C3N4-PDA-Ag@CS composite dressing has excellent antibacterial properties, biocompatibility, and enhances wound healing, thus providing a strategy for the application of photocatalytic materials for the treatment of infected wounds.

Redox and pH dual sensitive carboxymethyl chitosan functionalized polydopamine nanoparticles loaded with doxorubicin for tumor chemo-photothermal therapy.

The high expression of reduced glutathione (GSH) and low pH in tumor sites have encouraged new ideas for targeted drug release. The tumor microenvironment is a crucial target for studying the anti-tumor efficiency of photothermal therapy because the microenvironment plays a key role in cancer progression, local resistance, immune escaping, and metastasis. Herein, active mesoporous polydopamine nanoparticles loaded with doxorubicin and functionalized with N,N'-bis(acryloyl)cystamine (BAC) and cross-linked carboxymethyl chitosan (CMC) were used to induce simultaneous redox- and pH-sensitive activity to achieve photothermal enhanced synergistic chemotherapy. The inherent disulfide bonds of BAC were able to deplete glutathione, thus increasing the oxidative stress in tumor cells and enhancing the release of doxorubicin. Additionally, the imine bonds between CMC and BAC were stimulated and decomposed in the acidic tumor microenvironment, improving the efficiency of light conversion through exposure to polydopamine. Moreover, in vitro and in vivo investigations demonstrated that this nanocomposite exhibited improved selective doxorubicin release in conditions mimicking the tumor microenvironment and low toxicity towards non-cancerous tissues, suggesting there is high potential for the clinical translation of this synergistic chemo-photothermal therapeutic agent.

Delivery of curcumin by fucoidan-coated mesoporous silica nanoparticles: Fabrication, characterization, and in vitro release performance.

Mesoporous silica nanoparticles (MSN) are effective drug delivery carriers because of their adjustable large pore size and high porosity. In this study, complex nanoparticles containing disulfide bonds (SS) were designed and prepared as curcumin (Cur) carriers by using fucoidan (FUC) and MSN as the polymer matrix. The product was characterized using scanning electron microscopy, transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and an N2 adsorption and desorption test. When the mass ratio of MSN to FUC was 2:1, the nanospheres particle size was the smallest (295.6 ± 0.98 nm, -35.2 ± 0.8 mV). Furthermore, the curcumin encapsulation rate by MSN-Cur-SS-FUC was over 90%, and the cumulative release rate in 24 h was over 80% due to the combined effect of weak acidity and high glutathione concentration in the tumor site microenvironment. When the Cur concentration was 50 µg/mL, the cell viability of free Cur was 63.8%, the cell viability of MSN-Cur-SS-FUC was 14.5%, and the cell viability of MSN-SS-FUC at the same concentration remained above 74.6%. MSN-SS-FUC composite nanoparticles showed a good delivery of Cur, a lipid-soluble active compound, and provides a new delivery route for other lipid-soluble and poorly bioavailable active compounds.

Cellulose nanocrystal/calcium alginate-based porous microspheres for rapid hemostasis and wound healing.

Porous microsphere hemostatic materials, which possess rapid hemostatic, antibacterial, and wound healing-promotion properties, have key advantages over hemostatic dressings with a single hemostatic function. Using rod-shaped cellulose nanocrystals as the supporting framework, sodium alginate/cellulose nanocrystal porous microspheres (SA/CNC) were prepared using an inverse emulsion method. After SA/CNC self-assembly with the antibacterial polymer ε-polylysine, the hemostatic porous microspheres (PSLMs) showed high porosity, high liquid absorption capacity, and excellent coagulation properties. The in vitro and in vivo coagulation properties of PSLMs were evaluated and compared with those of the commercially available chitosan hemostatic powder. PSLMs had marked hemostatic effects in the following mouse hemorrhage models: caudal (81.20 s), liver (48.44 s), and femoral artery (71.66 s). After the introduction of ε-polylysine with excellent antibacterial properties to PSLMs, PSLMs effectively inhibited the activities of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

Efficient Delivery of Curcumin by Alginate Oligosaccharide Coated Aminated Mesoporous Silica Nanoparticles and In Vitro Anticancer Activity against Colon Cancer Cells.

We designed and synthesized aminated mesoporous silica (MSN-NH2), and functionally grafted alginate oligosaccharides (AOS) on its surface to get MSN-NH2-AOS nanoparticles as a delivery vehicle for the fat-soluble model drug curcumin (Cur). Dynamic light scattering, thermogravimetric analysis, and X-ray photoelectron spectroscopy were used to characterize the structure and performance of MSN-NH2-AOS. The nano-MSN-NH2-AOS preparation process was optimized, and the drug loading and encapsulation efficiencies of nano-MSN-NH2-AOS were investigated. The encapsulation efficiency of the MSN-NH2-Cur-AOS nanoparticles was up to 91.24 ± 1.23%. The pH-sensitive AOS coating made the total release rate of Cur only 28.9 ± 1.6% under neutral conditions and 67.5 ± 1% under acidic conditions. According to the results of in vitro anti-tumor studies conducted by MTT and cellular uptake assays, the MSN-NH2-Cur-AOS nanoparticles were more easily absorbed by colon cancer cells than free Cur, achieving a high tumor cell targeting efficiency. Moreover, when the concentration of Cur reached 50 µg/mL, MSN-NH2-Cur-AOS nanoparticles showed strong cytotoxicity against tumor cells, indicating that MSN-NH2-AOS might be a promising tool as a novel fat-soluble anticancer drug carrier.

Simultaneous determination of catecholamines and their metabolites related to Alzheimer's disease in human urine.

A simple and specific high-performance liquid chromatography method coupled with fluorescence detection (HPLC-FL) has been developed for the simultaneous determination of L-3,4-dihydroxyphenylalanine, norepinephrine, dopamine, epinephrine and 3,4-dihydroxyphenylacetic acid in human urine. The samples were derivatized by 1,2-diphenylethylenediamine with isoprenaline as internal standard. The factors affecting the fluorescence yield were investigated, including the reaction and separation conditions. The catecholamine derivatives were separated on a Kromasil C(18) column with methanol and sodium acetate buffer as mobile phase. The limits of detection for all catecholamines ranged from 0.2 to 1.1 ng/mL. The linear ranges were from 2.5 to 200 ng/mL except 3,4-dihydroxyphenylacetic acid from 5 to 200 ng/mL. The intra- and interday RSDs for all catecholamines were 1.0-8.0 and 2.1-14%, respectively. The method was successfully applied to determine the catecholamines in human urine from 14 Alzheimer's disease patients and 14 healthy volunteers. It was concluded that the mean levels of catecholamines in urine of Alzheimer's disease patients were all lower than those in healthy volunteers. The cluster analysis and independent samples T-test were used to distinguish the Alzheimer's disease patients and healthy volunteers.

Determination of Fucoxanthin in Bloom-Forming Macroalgae by HPLC-UV.

Fucoxanthin is a carotenoid natural product with extensive biological activities and offers a variety of health benefits. Brown algae and diatoms are known producers of this compound as an important component of their light-harvesting complexes. Considering its important function in algal photosynthesis, we assume that the massive biomass from macroalgal blooms is potential bioresources of this compound. Accordingly, a high-performance liquid chromatography-ultra-violet (HPLC-UV) method was developed and validated for quantitation of fucoxanthin in bloom-forming macroalgal species from coastal waters of north China. The linear regression was acquired with r = 0.9991. The precisions were evaluated by intra- and inter-day tests, and the relative standard deviation (RSD) values were within the range of 0.59 and 2.30%, respectively. The recoveries for the method were observed over the range of 99.3-100.4% with RSD values < 2.6%. Our results showed that fucoxanthin occurs in all the tested algae including red and green algal species, which are not generally considered as fucoxanthin producers. Application of HPLC-time-of-flight mass spectrometry for the qualitative analysis further confirmed the production of fucoxanthin in these species. The developed method provided an insight into the potential of the macroalgal biomass commercial production of fucoxanthin.