ABSTRACT
Different types of clinical wounds are difficult to treat while infected by bacteria. Wound repair involves multiple cellular and molecular interactions, which is a complicated process. However, wound repair often suffers from abnormal cellular functions or pathways that result in unavoidable side effects, so there is an urgent need for a material that can heal wounds quickly and with few side effects. Based on these needs, hydrogels with injectable properties have been confirmed to be able to undergo self-healing, which provides favorable conditions for wound healing. Notably, as a biopolymer with excellent easy-to-modify properties from a wide range of natural sources, chitosan can be used to prepare injectable hydrogel with multifunction for wound healing because of its outstanding flowability and injectability. Especially, chitosan-based hydrogels with marked biocompatibility, non-toxicity, and bio-adhesion properties are ideal for facilitating wound healing. In this review, the characteristics and healing mechanisms of different wounds are briefly summarized. In addition, the preparation and characterization of injectable chitosan hydrogels in recent years are classified. Additionally, the bioactive properties of this type of hydrogel in vitro and in vivo are demonstrated, and future trend in wound healing is prospected.
Subject(s)
Chitosan , Wound Healing , Hydrogels/pharmacology , Anti-Bacterial AgentsABSTRACT
Green tides, a globally prevalent marine ecological anomaly observed in coastal regions, have received substantial attention. However, there is limited research on the burial of Ulva prolifera in sediments during the late stages of green tide outbreaks. This study investigates the effect of temperature on U. prolifera buried in sediment over 30 days. The measurements included the length, biomass, relative growth rate, chlorophyll composition and maximum quantum yield (Fv/Fm) of PS II at different stages. The results indicate that at -20 °C, numerous seedlings emerged after 14 days of recovery culture, suggesting the release of spores or gametes; survival was possible from -2 °C to 15 °C; but at 20 °C and 30 °C, all U. prolifera died. The U. prolifera buried in sediment during the late stage of green tide outbreaks may serve as one of the sources for the subsequent year's green tide eruption. This research provides insights into the origins of green tide outbreaks in the southern Yellow Sea.
Subject(s)
Edible Seaweeds , Eutrophication , Ulva , Temperature , Biomass , ChinaABSTRACT
Anthocyanin is an important pigment that prevents oxidative stress and mediates adaptation of plants to salt stress. Peanuts with dark red and black testa are rich in anthocyanin. However, correlation between salt tolerance and anthocyanin content in black and dark red testa peanuts is unknown. In this study, three peanut cultivars namely YZ9102 (pink testa), JHR1 (red testa) and JHB1 (black testa) were subjected to sodium chloride (NaCl) stress. The plant growth, ion uptake, anthocyanin accumulation, oxidation resistance and photosynthetic traits were comparatively analyzed. We observed that the plant height, leaf area and biomass under salt stress was highly inhibited in pink color testa (YZ9102) as compare to black color testa (JHB1). JHB1, a black testa colored peanut was identified as the most salt-tolerance cultivar, followed by red (JHR1) and pink(YZ9102). During salt stress, JHB1 exhibited significantly higher levels of anthocyanin and flavonoid accumulation compared to JHR1 and YZ9102, along with increased relative activities of antioxidant protection and photosynthetic efficiency. However, the K+/Na+ and Ca2+/Na+ were consistently decreased among three cultivars under salt stress, suggesting that the salt tolerance of black testa peanut may not be related to ion absorption. Therefore, we predicted that salt tolerance of JHB1 may be attributed to the accumulation of the anthocyanin and flavonoids, which activated antioxidant protection against the oxidative damage to maintain the higher photosynthetic efficiency and plant growth. These findings will be useful for improving salt tolerance of peanuts.
ABSTRACT
To investigate the detrimental impacts of cyanobacterial bloom, specifically Microcystis aeruginosa, on brackish water ecosystems, the study used Moina mongolica, a cladoceran species, as the test organism. In a chronic toxicology experiment, the survival and reproductive rates of M. mongolica were assessed under M. aeruginosa stress. It was observed that the survival rate of M. mongolica fed with M. aeruginosa significantly decreased with time and their reproduction rate dropped to zero, while the control group remained maintained stable and normal reproduction. To further explore the underlying molecular mechanisms of the effects of M. aeruginosa on M. mongolica, we conducted a transcriptomic analysis on newly hatched M. mongolica cultured under different food conditions for 24 h. The results revealed significant expression differences in 572 genes, with 233 genes significantly up-regulated and 339 genes significantly down-regulated. Functional analysis of these differentially expressed genes identified six categories of physiological functional changes, including nutrition and metabolism, oxidative phosphorylation, neuroimmunology, cuticle and molting, reproduction, and programmed cell death. Based on these findings, we outlined the basic mechanisms of microcystin toxicity. The discovery provides critical insights into the mechanisms of Microcystis toxicity on organisms and explores the response mechanisms of cladocerans under the stress of Microcystis.
Subject(s)
Cladocera , Microcystis , Animals , Microcystis/physiology , Ecosystem , Gene Expression Profiling , Saline WatersABSTRACT
The development of nanoparticles loaded with natural active ingredients is one of the hot trends in the pharmaceutical industry. Herein, chitosan was selected as the base material, and sodium tripolyphosphate was chosen as the cross-linking agent. Chitosan nanoparticles loaded with ß-acids from hops were prepared by the ionic cross-linking method. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that chitosan nanoparticles successfully encapsulated ß-acids. The loading capacity of chitosan nanoparticles with ß-acids was 2.00 %-18.26 %, and the encapsulation efficiency was 0.58 %-55.94 %. Scanning electron microscopy (SEM), transmission electron microscope (TEM), particle size, and zeta potential results displayed that the nanoparticles revealed a sphere-like distribution with a particle size range of 241-261 nm, and the potential exhibited positive potential (+14.47-+16.27 mV). The chitosan nanoparticles could slowly release ß-acids from different simulated release media. Notably, the ß-acids-loaded nanoparticles significantly inhibited Staphylococcus aureus ATCC25923 (S. aureus) and Escherichia coli ATCC25922 (E. coli). Besides, ß-acids-loaded chitosan nanoparticles were cytotoxic to colorectal cancer cells (HT-29 and HCT-116). Therefore, applying chitosan nanoparticles can further expand the application of ß-acids in biomedical fields.
Subject(s)
Chitosan , Nanoparticles , Polyphosphates , Chitosan/chemistry , Delayed-Action Preparations/pharmacology , Staphylococcus aureus , Escherichia coli , Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistry , Particle Size , Spectroscopy, Fourier Transform Infrared/methodsABSTRACT
Golden tide outbreak threatened the marine ecological environment. Sargassum horneri is a single dominant species of the Yellow Sea golden tide, which growth and development are affected by changes in sea water temperature. This study investigated the photosynthetic physiology of copper algae and found that the growth rate, chlorophyll a content, carotenoid content, Fv/Fm, and maximum electron transfer efficiency were significantly reduced, indicating that Sargassum horneri was under stress under high temperature. In this study, high-throughput sequencing was used to analyze the response mechanisms of photosynthesis-related genes in S. horneri under high temperature stress. The results showed that most of the photosynthesis-related genes in S. horneri were downregulated and photosynthesis was inhibited under high temperature stress. However, the expression levels of ferredoxin, ferredoxin-NADP reductase, light-harvesting protein complexes, and oxygen-evolving complex genes were significantly upregulated (P ≤ 0.05) after five days of high temperature treatment. This study found that photosynthesis related genes play a crucial role in regulating the photosynthetic response of S. horneri to high temperature stress.
Subject(s)
Sargassum , Temperature , Chlorophyll A , Photosynthesis , SeawaterABSTRACT
The role of regenerative medicine in clinical therapies is becoming increasingly vital. Under specific conditions, mesenchymal stem cells (MSCs) are capable of differentiating into mesoblastema (i.e., adipocytes, chondrocytes, and osteocytes) and other embryonic lineages. Their application in regenerative medicine has attracted a great deal of interest among researchers. To maximize the potential applications of MSCs, materials science could provide natural extracellular matrices and provide an effective means to understand the various mechanisms of differentiation for the growth of MSCs. Pharmaceutical fields are represented among the research on biomaterials by macromolecule-based hydrogel nanoarchitectonics. Various biomaterials have been used to prepare hydrogels with their unique chemical and physical properties to provide a controlled microenvironment for the culture of MSCs, laying the groundwork for future practical applications in regenerative medicine. This article currently describes and summarizes the sources, characteristics, and clinical trials of MSCs. In addition, it describes the differentiation of MSCs in various macromolecule-based hydrogel nanoarchitectonics and highlights the preclinical studies of MSCs-loaded hydrogel materials in regenerative medicine conducted over the past few years. Finally, the challenges and prospects of MSC-loaded hydrogels are discussed, and the future development of macromolecule-based hydrogel nanoarchitectonics is outlined by comparing the current literature.
Subject(s)
Mesenchymal Stem Cells , Regenerative Medicine , Hydrogels/pharmacology , Hydrogels/chemistry , Biocompatible Materials/pharmacology , Cell DifferentiationABSTRACT
Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.
ABSTRACT
BACKGROUND: Testa color is an important trait of peanut (Arachis hypogaea L.) which is closely related with the nutritional and commercial value. Pink and red are main color of peanut testa. However, the genetic mechanism of testa color regulation in peanut is not fully understood. To elucidate a clear picture of peanut testa regulatory model, samples of pink cultivar (Y9102), red cultivar (ZH12), and two RNA pools (bulk red and bulk pink) constructed from F4 lines of Y9102 x ZH12 were compared through a bulk RNA-seq approach. RESULTS: A total of 2992 differential expressed genes (DEGs) were identified among which 317 and 1334 were up-regulated and 225 and 1116 were down-regulated in the bulk red-vs-bulk pink RNA pools and Y9102-vs-ZH12, respectively. KEGG analysis indicates that these genes were divided into significantly enriched metabolic pathways including phenylpropanoid, flavonoid/anthocyanin, isoflavonoid and lignin biosynthetic pathways. Notably, the expression of the anthocyanin upstream regulatory genes PAL, CHS, and CHI was upregulated in pink and red testa peanuts, indicating that their regulation may occur before to the advent of testa pigmentation. However, the differential expression of down-stream regulatory genes including F3H, DFR, and ANS revealed that deepening of testa color not only depends on their gene expression bias, but also linked with FLS inhibition. In addition, the down-regulation of HCT, IFS, HID, 7-IOMT, and I2'H genes provided an alternative mechanism for promoting anthocyanin accumulation via perturbation of lignin and isoflavone pathways. Furthermore, the co-expression module of MYB, bHLH, and WRKY transcription factors also suggested a fascinating transcriptional activation complex, where MYB-bHLH could utilize WRKY as a co-option during the testa color regulation by augmenting anthocyanin biosynthesis in peanut. CONCLUSIONS: These findings reveal candidate functional genes and potential strategies for the manipulation of anthocyanin biosynthesis to improve peanut varieties with desirable testa color.
Subject(s)
Anthocyanins , Arachis , Anthocyanins/metabolism , Arachis/genetics , Arachis/metabolism , Gene Regulatory Networks , Lignin/metabolism , Pigmentation/genetics , Gene Expression Regulation, Plant , Color , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression ProfilingABSTRACT
Green tides have occurred in the Southern Yellow Sea (SYS) for 16 consecutive years, causing widespread concern. Attached and floating green macroalgae have been observed in Binhai Harbor, Jiangsu Province, China, in the SYS. This study used morphological analysis, and internal transcribed spacers and rps2-trnL molecular identification methods, to analyze the species composition and biomass of green macroalgae along the Binhai Harbor coast. Six species of green tide algae (Ulva prolifera, Ulva meridionalis, Ulva linza, Ulva flexuosa, Ulva californica, and Ulva intestinalis) were identified, in addition to Blidingia sp. The discovery of U. californica is the first report of this species off the coast of Jiangsu Province. The floating green macroalgae along the Binhai Harbor coast originated from attached green macroalgae in Binhai Harbor, and a small number of the attached algae were closely related to the large-scale floating U. prolifera in the SYS. Moreover, in December 2021, February 2022, and April 2022, the total biomass of attached green macroalgae in Binhai Harbor was 25.600, 10.767, and 25.867 t, respectively, of which the U. prolifera biomass was 10.697, 8.709, and 4.185 t, respectively. This study proved Binhai Harbor may not be an important source of green tide in the SYS.
Subject(s)
Chlorophyta , Seaweed , Ulva , Biomass , Eutrophication , ChinaABSTRACT
KEY MESSAGE: The candidate gene AhLBA1 controlling lateral branch angel of peanut was fine-mapped to a 136.65-kb physical region on chromosome 15 using the BSA-seq and QTL mapping. Lateral branch angel (LBA) is an important plant architecture trait of peanut, which plays key role in lodging, peg soil penetration and pod yield. However, there are few reports of fine mapping and quantitative trait loci (QTLs)/cloned genes for LBA in peanut. In this project, a mapping population was constructed using a spreading variety Tifrunner and the erect variety Fuhuasheng. Through bulked segregant analysis sequencing (BSA-seq), a major gene related to LBA, named as AhLBA1, was preliminarily mapped at the region of Chr.15: 150-160 Mb. Then, using traditional QTL approach, AhLBA1 was narrowed to a 1.12 cM region, corresponding to a 136.65-kb physical interval of the reference genome. Of the nine genes housed in this region, three of them were involved in hormone metabolism and regulation, including one "F-box protein" and two "2-oxoglutarate (2OG) and Fe(II)-dependent oxygenase (2OG oxygenase)" encoding genes. In addition, we found that the level of some classes of cytokinin (CK), auxin and ethylene showed significant differences between spreading and erect peanuts at the junction of main stem and lateral branch. These findings will aid further elucidation of the genetic mechanism of LBA in peanut and facilitating marker-assisted selection (MAS) in the future breeding program.
Subject(s)
Arachis , Quantitative Trait Loci , Arachis/genetics , Plant Breeding , Chromosome Mapping , Phenotype , Oxygenases/geneticsABSTRACT
Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.
Subject(s)
Curcumin , Nanoparticles , Neoplasms , Animals , Cell Line, Tumor , Collagen , Curcumin/chemistry , Drug Delivery Systems , Losartan , Matrix Metalloproteinases/metabolism , Mice , Nanoparticle Drug Delivery System , Nanoparticles/chemistry , Neoplasms/drug therapy , Particle Size , Polyesters/chemistry , Tumor MicroenvironmentABSTRACT
A series of novel galactoside derivatives containing 1,3,4-thiadiazole moiety were synthesized, and the structure of them was verified by spectroscopy of NMR and HRMS, and antifungal and antibacterial activities of them were screened. The results showed that the newly synthesized compounds had good antifungal activities. Among them, â ¢16, â ¢17, and â ¢19 exhibited satisfactory activities against Phytophthora infestans (P. infestans), with EC50 values of 5.87, 4.98, and 6.17 µg/ml, respectively, which were similar to those of dimethomorph (5.52 µg/ml). Meanwhile, the title compounds also possessed certain antibacterial activities.
ABSTRACT
Lateral branch angle (LBA), or branch habit, is one of the most important agronomic traits in peanut. To date, the underlying molecular mechanisms of LBA have not been elucidated in peanut. To acquire the differentially expressed genes (DEGs) related to LBA, a TI population was constructed through the hybridization of a bunch-type peanut variety Tifrunner and prostrate-type Ipadur. We report the identification of DEGs related to LBA by sequencing two RNA pools, which were composed of 45 F3 lines showing an extreme opposite bunch and prostrate phenotype. We propose to name this approach Bulk RNA-sequencing (BR-seq) as applied to several plant species. Through BR-seq analysis, a total of 3083 differentially expressed genes (DEGs) were identified, including 13 gravitropism-related DEGs, 22 plant hormone-related DEGs, and 55 transcription factors-encoding DEGs. Furthermore, we also identified commonly expressed alternatively spliced (AS) transcripts, of which skipped exon (SE) and retained intron (RI) were most abundant in the prostrate and bunch-type peanut. AS isoforms between prostrate and bunch peanut highlighted important clues to further understand the post-transcriptional regulatory mechanisms of branch angle regulation. Our findings provide not only important insights into the landscape of the regulatory pathway involved in branch angle formation but also present practical information for peanut molecular breeding in the future.
Subject(s)
Arachis , Transcriptome , Arachis/genetics , Arachis/metabolism , RNA/metabolism , RNA-Seq , Sequence Analysis, RNAABSTRACT
Peanut is one of the most important cash crops with high quality oil, high protein content, and many other nutritional elements, and grown globally. Cultivated peanut (Arachis hypogaea L.) is allotetraploid with a narrow genetic base, and its genetics and molecular mechanisms controlling the agronomic traits are poorly understood. Here, we report a comprehensive genome variation map based on the genotyping of a panel of 178 peanut cultivars using Axiom_Arachis2 SNP array, including 163 representative varieties of different provinces in China, and 15 cultivars from 9 other countries. According to principal component analysis (PCA) and phylogenetic analysis, the peanut varieties were divided into 7 groups, notable genetic divergences between the different areas were shaped by environment and domestication. Using genome-wide association study (GWAS) analysis, we identified several marker-trait associations (MTAs) and candidate genes potentially involved in regulating several agronomic traits of peanut, including one MTA related with hundred seed weight, one MTA related with total number of branches, and 14 MTAs related with pod shape. This study outlines the genetic basis of these peanut cultivars and provides 13,125 polymorphic SNP markers for further distinguishing and utility of these elite cultivars. In addition, the candidate loci and genes provide valuable information for further fine mapping of QTLs and improving the quality and yield of peanut using a genomic-assisted breeding method.
ABSTRACT
BACKGROUND & AIMS: Genetic factors underlie a substantial proportion of paediatric liver diseases. Hereditary liver diseases have considerable genetic heterogeneity and variable clinical manifestations, which bring great challenges to clinical and molecular diagnoses. In this study, we investigated a group of paediatric patients with varying degrees of liver dysfunction using a hierarchical genetic testing strategy. METHODS: We first applied a panel encompassing 166 known causal genes of liver disease. We then used exome sequencing (ES) in those patients whose cases remained undiagnosed to identify the genetic aetiology of their symptoms. RESULTS: In total, we enrolled 131 unrelated paediatric patients with liver disease of Chinese Han ethnicity. We first applied targeted gene sequencing of 166 genes to all patients and yielded a diagnostic rate of 35.9% (47 of 131). Eighty-four patients who remained undiagnosed after target gene sequencing were subjected to ES. As a result, eight (8/84, 9.5%) of them obtained molecular diagnoses, including four patients suspected of abnormal bilirubin metabolism and four idiopathic cases. Non-typical genetic findings, including digenic inheritance and dual molecular diagnosis, were also identified. Through a comprehensive assessment of novel candidate variants of uncertain disease association, 11 patients of the remaining undiagnosed patients were able to obtain likely molecular diagnoses. CONCLUSIONS: Our study presents evidence for the diagnostic utility of sequential genetic testing in a cohort of patients with paediatric liver disease. Our findings expand the understanding of the phenotypic and mutational spectrum underlying this heterogeneous group of diseases.
Subject(s)
Exome , Liver Diseases , Child , Genetic Testing , Humans , Liver Diseases/diagnosis , Liver Diseases/genetics , Mutation , Exome SequencingABSTRACT
Studies have shown that high-density lipoprotein (HDL) is a powerful anti-atherosclerosis factor in vivo and in vitro, with anti-inflammatory effects, and it also plays an important role in the immune system and central nervous system (CNS). In this study, the BV2 microglia inflammation model and experimental autoimmune encephalomyelitis animal model were used to investigate the potential mechanism of HDL in multiple sclerosis. Our results show that HDL inhibits the activation of BV2 microglia in a model of BV2 microglia inflammation and were validated with primary microglia. HDL can down-regulate the expression of TNF-α, IL-6, iNOS and NO. Western blot results showed that HDL could reduce the expression levels of TLR4, CD14, MyD88 and NF-κB p65 LPS-induced microglia. In a mouse model of experimental autoimmune encephalomyelitis, hematoxylin-eosin (HE) staining showed decreased infiltration of inflammatory cells in brain and spinal cord tissues, and Luxol Fast Blue (LFB) staining showed significant improvement in spinal cord demyelination. We found that HDL reduced spinal cord and brain inflammation after EAE induction, inhibited the infiltration of CD68 and Iba-1 positive inflammatory cells, and reduced the production of multiple pro-inflammatory cytokines, including pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. Western blot showed that EAE mice HDL inhibited the activation of ERK1/2 and JNK in MAPK pathway and p-IκBα and P65 in NF-κB pathway. Taken together, our study suggests that HDL may influence microglia activation and inflammatory response in mice by regulating inflammatory signaling pathways, improving induction of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and provides further insights into HDL therapy for multiple sclerosis.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Animals , Lipoproteins, HDL/metabolism , Lipoproteins, HDL/pharmacology , Mice , Mice, Inbred C57BL , Microglia , NF-kappa B/metabolismABSTRACT
BACKGROUND/OBJECTIVE: Periodontitis is a widely spread oral infection and various antibiotics are utilized for its treatment, but high oral doses and development of antibiotic resistance limit their use. This study was aimed at development of natural polymer-based mucoadhesive bilayer films loaded with moxifloxacin hydrochloride (Mox) and clove essential oil (CEO) to potentially combat bacterial infection associated with periodontitis. METHODS: Films were synthesized by double solvent casting technique having an antibiotic in the gellan gum-based primary layer with clove oil in a hydroxyethyl cellulose-based secondary layer. RESULTS: Prepared films were transparent, flexible, and showed high antibacterial response against both gram-positive and gram-negative bacteria. The films showed excellent pharmaceutical attributes in terms of drug content, folding endurance, swelling index, and mucoadhesive strength. Solid state characterization of formulation showed successful incorporation of drug and oil in separate layers of hydrogel structure. An in-vitro release study showed an initial burst release of drug followed by sustained release for up to 48 hours. CONCLUSION: The prepared mucoadhesive bilayer buccal films could be used as a potential therapeutic option for the management of periodontitis.
Subject(s)
Anti-Bacterial Agents/pharmacology , Clove Oil/pharmacology , Moxifloxacin/pharmacology , Polysaccharides, Bacterial/chemistry , Adhesiveness , Administration, Buccal , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Chemistry, Pharmaceutical/methods , Clove Oil/administration & dosage , Delayed-Action Preparations , Drug Liberation , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Moxifloxacin/administration & dosage , Moxifloxacin/chemistry , Oils, Volatile/administration & dosage , Oils, Volatile/pharmacology , Periodontitis/drug therapy , Periodontitis/microbiologyABSTRACT
Chemotherapeutic treatments are indispensable in the treatment of breast cancer. However, the emergence of multidrug-resistance, strong cell toxicity, and poor targeting selection has inhibited their clinical application. In this study, two synergistic drugs, doxorubicin (DOX) and curcumin (CUR), were co-administered to overcome multidrug resistance (MDR). Based on the characteristics of the tumor microenvironment, we developed folic acid-modified nanoparticles ((DOX + CUR)-FA-NPs) based on a star-shaped polyester (FA-TRI-CL) to enhance the tumor targeting selectivity and drug loading (DL) capacity. The (DOX + CUR)-FA-NPs displayed a characteristic spheroid morphology with an ideal diameter (186.52 nm), polydispersity index (0.024), zeta potential (-18.87 mV), and good entrapment efficiency (97.64%/78.13%, DOX/CUR) and DL (20.27%/11.29%, DOX/CUR) values. In vitro pharmacokinetic and pharmacodynamic experiments demonstrated that the (DOX + CUR)-FA-NPs were gradually released, and they displayed the highest cell apoptosis and cellular uptake in MCF-7/ADR cells. Additionally, in vivo results illustrated that (DOX + CUR)-FA-NPs not only displayed significant tumor targeting and anticancer efficacy, but also induced less pathological damage to the normal tissue. In summary, co-administered DOX and CUR appeared to reverse MDR, and this targeted combinational nanoscale delivery system could thus be a promising carrier for tumor therapies in the future.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Curcumin/pharmacology , Doxorubicin/pharmacology , Nanoparticles/chemistry , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Cell Survival/drug effects , Chemistry, Pharmaceutical , Curcumin/administration & dosage , Curcumin/pharmacokinetics , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Drug Carriers/chemistry , Drug Combinations , Drug Liberation , Drug Resistance, Neoplasm/drug effects , Female , Folic Acid/chemistry , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Particle Size , Polyesters/chemistry , Surface Properties , Tumor MicroenvironmentABSTRACT
PURPOSE: A novel folate receptor-targeted ß-cyclodextrin (ß-CD) drug delivery vehicle was constructed to improve the bioavailability, biosafety, and drug loading capacity of curcumin. Controlled release and targeted delivery was achieved by modifying the nanoparticles with folic acid (FA). METHODS: Folate-conjugated ß-CD-polycaprolactone block copolymers were synthesized and characterized. Curcumin-loaded nanoparticles (FA-Cur-NPs) were structured by self-assembly. The physicochemical properties, stability, release behavior and tumor-targeting ability of the fabricated nanoparticles were studied. RESULTS: The average particle size and drug loading of FA-Cur-NPs was 151.8 nm and 20.27%, respectively. Moreover, the FA-Cur-NPs exhibited good stability in vitro for 72 h. The drug release profiles showed that curcumin from FA-Cur-NPs was released significantly faster in a pH 6.4 phosphate buffered solution (PBS) than in pH 7.4, indicating that curcumin can be enriched around the tumor site compared with normal cells. Additionally, the internalization of FA-Cur-NPs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. Furthermore, in vivo studies confirmed that FA-Cur-NPs exhibited marked accumulation in the tumor site and excellent antitumor activity. CONCLUSION: These findings suggest that FA-Cur-NPs are a promising approach for improving cancer therapy through active targeting and controllable release.