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1.
Int J Biol Macromol ; 268(Pt 2): 131915, 2024 May.
Article in English | MEDLINE | ID: mdl-38679254

ABSTRACT

A water-soluble polysaccharide from the brown alga Ishige Okamurae, designated IOP-0, was obtained by preparative anion-exchange and size-exclusion chromatography. Chemical and spectroscopic investigations revealed that IOP-0 was a sulfated fucoidan with a backbone primarily composed of 3-linked and 4-linked-L-fucose with sulfate groups at C-2/C-4 of the 3-linked-L-fucose. The protective effect of IOP-0 on ulcerative colitis was evaluated in this work. The results showed that IOP-0 could significantly alleviate the symptoms of ulcerative colitis by preventing weight loss, preserving the structure of intestinal tissues, and ameliorating the dysregulation of inflammatory cytokines (TNF-α, IL-6, and IL-10). Meanwhile, IOP-0 protected the colonic mucosal barrier by promoting the tight junction protein ZO-1 and occludin expression. In addition, IOP-0 was able to maintain intestinal homeostasis and improve intestinal function by regulating the gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs). These results suggest that IOP-0 might be a potential dietary supplement for the prevention and treatment of ulcerative colitis.


Subject(s)
Colitis, Ulcerative , Dextran Sulfate , Gastrointestinal Microbiome , Polysaccharides , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Polysaccharides/pharmacology , Polysaccharides/chemistry , Animals , Gastrointestinal Microbiome/drug effects , Dextran Sulfate/adverse effects , Mice , Phaeophyceae/chemistry , Cytokines/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Inflammation/drug therapy , Sulfates/chemistry , Male
2.
Int J Biol Macromol ; 267(Pt 1): 131214, 2024 May.
Article in English | MEDLINE | ID: mdl-38580029

ABSTRACT

This study aimed to investigate the physicochemical properties of soluble dietary fiber (SDF) and cellulose enriched in Saccharina japonica by-products and to evaluate their anti-colitis effects. The water-holding capacity (WHC), swelling capacity (SC), cation exchange capacity (CEC), and antioxidant properties of SDF were superior to cellulose. The ΔH of SDF and cellulose was 340.73 J/g and 134.56 J/g, and the average particle size of them was 43.858 µm and 97.350 µm. The viscosity of SDF was positively correlated with the content. SEM revealed that the microstructure of SDF was porous, whereas cellulose was folded. SDF contained seven monosaccharides such as mannuronic acid and mannose, while cellulose had a single glucose composition. It was also shown that both SDF and cellulose reversed the pathological process of colitis by inhibiting weight loss, preventing colon injury, balancing oxidative stress, and regulating the level of inflammation, with the optimal dose being 1.5 g/kg. The difference was that SDF inhibited the expression of NF-кB and TNF-α, while cellulose up-regulated the expression of PPAR-γ and IL-10. Additionally, SDF could more positively control the expression of ZO-1, whereas cellulose was superior in improving the expression of Occludin. Interestingly, SDF could restore the structure of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group to ameliorate ulcerative colitis (UC), whereas cellulose mainly regulated the abundance of norank_f_Muribaculaceae, Faecalibaculum, Bacteroides and unclassified_f__Lachnospiraceae. The production of short-chain fatty acids (SCFAs) was also found to be restored by SDF and cellulose. Overall, SDF and cellulose can be considered important dietary components for treating and preventing UC.


Subject(s)
Cellulose , Colitis , Dietary Fiber , Edible Seaweeds , Gastrointestinal Microbiome , Laminaria , Cellulose/pharmacology , Animals , Gastrointestinal Microbiome/drug effects , Mice , Dietary Fiber/pharmacology , Colitis/metabolism , Colitis/chemically induced , Fatty Acids, Volatile/metabolism , Male , Solubility , Inflammation/metabolism , Antioxidants/pharmacology , Oxidative Stress/drug effects , Disease Models, Animal
3.
Int J Mol Sci ; 24(20)2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37894736

ABSTRACT

Although it is well recognized that mycosporine-like amino acids (MAAs) are ultraviolet (UV) protective agents that can reduce UV damage, the specific biological mechanism of its role in the skin remains unclear. In this study, we investigated the effect of MAAs extracted from Antarctic diatom Phaeodactylum tricornutum ICE-H on UVB-induced skin damage using a mice model. The MAAs components identified by liquid chromatography-tandem mass spectrometry included 4-deoxygadusol, shinorine, and porphyra-334, which were purified using a Supledean Carboxen1000 solid phase extraction column. The antioxidant activities of these MAA compounds were tested in vitro. For UVB-induced skin photodamage in mice, MAAs alleviated skin swelling and epidermal thickening in this study. We detected the content of reactive oxygen species (ROS), malondialdehyde, and collagen in skin tissue. In addition, quantitative real-time polymerase chain reaction was used to detect nuclear factor-κB (NF-κB), tumor necrosis factor α, interleukin-1ß, cyclooxygenase-2, mitogen activated protein kinase (MAPK) family (extracellular signal-regulated kinase, c-Jun amino-terminal kinase, and p38 kinase), and matrix metalloproteinases. The expression of these cytokines and enzymes is related to inflammatory responses and collagen degradation. In comparison to the model group without MAA treatment, the MAA component decreased the concentration of ROS, the degree of oxidative stress in the skin tissue, and the expression of genes involved in the NF-κB and MAPK pathways. In summary, these MAA components extracted from Phaeodactylum tricornutum ICE-H protected against UVB-induced skin damage by inhibiting ROS generation, relieving skin inflammation, and slowing down collagen degradation, suggesting that these MAA components are effective cosmetic candidate molecules for the protection and therapy of UVB damage.


Subject(s)
Amino Acids , Diatoms , Animals , Mice , Amino Acids/chemistry , Diatoms/metabolism , Reactive Oxygen Species/metabolism , NF-kappa B/metabolism , Antarctic Regions , Skin/metabolism , Mitogen-Activated Protein Kinases/metabolism , Collagen/pharmacology , Ultraviolet Rays/adverse effects
4.
Int J Mol Sci ; 24(18)2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37762273

ABSTRACT

The previous study successfully established an expression strain of ζ-carotene-like compounds (CLC) and demonstrated its remarkable antioxidant activity, which exhibited resistance to photodamage caused by UVB radiation on the skin following gavage administration. The objective of this study was to investigate the impact and mechanism of CLC on UVB-induced skin damage through topical application. Cell viability, anti-apoptotic activity, ROS scavenging ability, the inhibition of melanin synthesis, the regulation of inflammatory factors and collagen deposition were assessed in cells and mice using qRT-PCR, WB, Elisa assays, immunohistochemistry staining and biochemical kits, etc. The experimental results demonstrated that CLC-mitigated apoptosis induced by UVB irradiation up-regulated the Keap1/Nrf2/ARE antioxidant pathway to attenuate levels of ROS and inflammatory factors (NF-κB, TNF-α, IL-6 and IL-ß), and suppressed MAPK/AP-1 and CAMP/PKA/CREB signaling pathways to mitigate collagen degradation, skin aging and melanin formation. In conclusion, this study underscored the potential of CLC as a safe and efficacious source of antioxidants, positioning it as a promising ingredient in the formulation of cosmetics targeting anti-aging, skin brightening and sunburn repair.

5.
Food Funct ; 14(18): 8331-8350, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37606633

ABSTRACT

ζ-Carotene is a key intermediate in the carotenoid pathway, but owing to its low content and difficulties in isolation, its application is restricted. In this study, three genes (pnCrtE, pnCrtB, and pnCrtP) in the carotenoid pathway of Antarctic moss were identified, recombined, and expressed in Escherichia coli (E. coli) BL21(DE3). The expression product was identified as one of the ζ-carotenes by UV absorbance spectrum, thin layer chromatography (TLC), and super-high-performance liquid chromatography-mass spectrum (UPLC-MS), and was called a ζ-carotene-like compound (CLC). Excessive exposure to ultraviolet B (UVB) irradiation is one of the main risk factors for skin photodamage. The purpose of this study was to investigate the preventive and therapeutic effects of CLC on UVB-induced skin photodamage in mice. In this paper, through histological examinations (hematoxylin-eosin, HE; Masson and TdT-mediated dUTP Nick-End Labeling, Tunel), biochemical index detection (reactive oxygen species, ROS; inflammatory factors; cyclobutyl pyrimidine dimers, CPDs and hyaluronic acid, HA), quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and intestinal content flora, etc., it is concluded that CLC has the potential to enhance skin antioxidant capacity by activating the nuclear transcription factor/antioxidant reaction element (Nrf2/ARE) pathway and also reduce skin inflammation and aging by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Moreover, the regulation of intestinal flora may potentially mitigate skin damage induced by UVB radiation. This research not only developed a green and sustainable platform for the efficient synthesis of CLC but also laid a foundation for its application in functional food and medicine for skin resistance against UVB damage.


Subject(s)
Gastrointestinal Microbiome , zeta Carotene , Animals , Mice , Antioxidants , Chromatography, Liquid , Escherichia coli , Tandem Mass Spectrometry , Inflammation , Carotenoids
6.
BMC Plant Biol ; 23(1): 399, 2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37605165

ABSTRACT

The environment in Antarctica is characterized by low temperature, intense UVB and few vegetation types. The Pohlia nutans M211 are bryophytes, which are the primary plants in Antarctica and can thrive well in the Antarctic harsh environment. The transcriptional profiling of Pohlia nutans M211 under low temperature and high UVB conditions was analyzed to explore their polar adaptation mechanism in the extreme Antarctic environment by third-generation sequencing and second-generation sequencing. In comparison to earlier second-generation sequencing techniques, a total of 43,101 non-redundant transcripts and 10,532 lncRNA transcripts were obtained, which were longer and more accurate. The analysis results of GO, KEGG, AS (alternative splicing), and WGCNA (weighted gene co-expression network analysis) of DEGs (differentially expressed genes), combined with the biochemical kits revealed that antioxidant, secondary metabolites pathways and photosynthesis were the key adaptive pathways for Pohlia nutans M211 to the Antarctic extreme environment. Furthermore, the low temperature and strong UVB are closely linked for the first time by the gene HY5 (hlongated hypocotyl 5) to form a protein interaction network through the PPI (protein-protein interaction networks) analysis method. The UVR8 module, photosynthetic module, secondary metabolites synthesis module, and temperature response module were the key components of the PPI network. In conclusion, this study will help to further explore the polar adaptation mechanism of Antarctic plants represented by bryophytes and to enrich the polar gene resources.


Subject(s)
Bryophyta , Bryopsida , Antioxidants , Antarctic Regions , Photosynthesis , Bryophyta/genetics
7.
Int J Biol Macromol ; 236: 123948, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36898463

ABSTRACT

A sulfated polysaccharide from the brown alga Ishige okamurae Yendo, designated IOY, was successfully isolated by anion-exchange and size-exclusion chromatography. Chemical and spectroscopic analyses demonstrated that IOY was a fucoidan, that consisted of →3)-α-l-Fucp-(1→, →4)-α-l-Fucp-(1→, →6)-ß-d-Galp-(1 â†’ and →3)-ß-d-Galp-(1 â†’ residues with sulfate groups at C-2/C-4 the of (1 â†’ 3)-α-l-Fucp and C-6 the of (1 â†’ 3)-ß-d-Galp residues. IOY possessed a potent immunomodulatory effect in vitro as measured by lymphocyte proliferation assay. The immunomodulatory effect of IOY was further investigated in vivo using immunosuppressed mice induced by cyclophosphamide (CTX). The results showed that IOY significantly increased the spleen and thymus indexes and alleviated CTX-induced spleen and thymus damage. Furthermore, IOY had a significant effect on hematopoietic function recovery and promoted the secretion of interleukin-2 (IL-2) and tumor necrosis factor (TNF-α). Notably, IOY reversed CD4+ and CD8+ T cell reduction and improved immune response. These data indicated that IOY had vital in immunomodulatory function and could be used as drug or functional food to lessen chemotherapy-induced immunosuppression.


Subject(s)
Phaeophyceae , Sulfates , Mice , Animals , Sulfates/chemistry , Polysaccharides/chemistry , Phaeophyceae/chemistry , Immunosuppression Therapy
8.
Int J Mol Sci ; 24(5)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36902109

ABSTRACT

κ-Selenocarrageenan (KSC) is an organic selenium (Se) polysaccharide. There has been no report of an enzyme that can degrade κ-selenocarrageenan to κ-selenocarrageenan oligosaccharides (KSCOs). This study explored an enzyme, κ-selenocarrageenase (SeCar), from deep-sea bacteria and produced heterologously in Escherichia coli, which degraded KSC to KSCOs. Chemical and spectroscopic analyses demonstrated that purified KSCOs in hydrolysates were composed mainly of selenium-galactobiose. Organic selenium foods through dietary supplementation could help regulate inflammatory bowel diseases (IBD). This study discussed the effects of KSCOs on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57BL/6 mice. The results showed that KSCOs alleviated the symptoms of UC and suppressed colonic inflammation by reducing the activity of myeloperoxidase (MPO) and regulating the unbalanced secretion of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10). Furthermore, KSCOs treatment regulated the composition of gut microbiota, enriched the genera Bifidobacterium, Lachnospiraceae_NK4A136_group and Ruminococcus and inhibited Dubosiella, Turicibacter and Romboutsia. These findings proved that KSCOs obtained by enzymatic degradation could be utilized to prevent or treat UC.


Subject(s)
Carrageenan , Colitis, Ulcerative , Gastrointestinal Microbiome , Organoselenium Compounds , Animals , Mice , Colitis, Ulcerative/prevention & control , Colitis, Ulcerative/therapy , Dextran Sulfate , Disease Models, Animal , Gastrointestinal Microbiome/drug effects , Interleukin-6/metabolism , Mice, Inbred C57BL , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Oligosaccharides/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Carrageenan/pharmacology , Carrageenan/therapeutic use , Organoselenium Compounds/pharmacology , Organoselenium Compounds/therapeutic use
9.
Int J Biol Macromol ; 226: 1319-1331, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36511265

ABSTRACT

The effects of soluble dietary fiber (SDF) and cellulose (IDF) from Saccharina japonica by-product and their differences in improving constipation were further clarified in the present study. We demonstrated that SDF was mainly made up of d-mannuronic acid and d-mannose while IDF consisted of d-glucose , which is different from other reported dietary fibers of terrestrial plants. In this research, both SDF and IDF improved fecal-related indicators, gastrointestinal transit rate and histological morphology in Lop-induced mice. Moreover, they could increase the level of antioxidant enzymes (SOD and GSH-Px), restore the expression of enteric neurotransmitters, and maintain the function of ZO-1, JAM-1 as well as Occludin. Interestingly, SDF and IDF had a significant up-regulated effect on the proportion of Muribaculacea, Prevotellaceaen and Lachnospiraceae, which are critical to preserving intestinal immune homeostasis. Besides, they promoted the biosynthesis of short-chain fatty acids (SCFAs). The overall index showed that SDF is more effective for constipation due to its better water retention capacity. Thus, they can be used as a safe dietary supplement for the treatment of chronic or occasional constipation in humans.


Subject(s)
Gastrointestinal Microbiome , Phaeophyceae , Humans , Mice , Animals , Cellulose/pharmacology , Loperamide , Constipation/chemically induced , Constipation/drug therapy , Dietary Fiber/pharmacology , Dietary Fiber/metabolism , Fatty Acids, Volatile/metabolism , Neurotransmitter Agents , Phaeophyceae/metabolism
10.
Mar Drugs ; 20(4)2022 Mar 24.
Article in English | MEDLINE | ID: mdl-35447896

ABSTRACT

An immunomodulatory polysaccharide (DAP4) was extracted, purified, and characterized from Durvillaea antarctica. The results of chemical and spectroscopic analyses demonstrated that the polysaccharide was a fucoidan, and was mainly composed of (1→3)-α-l-Fucp and (1→4)-α-l-Fucp residues with a small degree of branching at C-3 of (1→4)-α-l-Fucp residues. Sulfate groups were at C-4 of (1→3)-α-l-Fucp, C-2 of (1→4)-α-l-Fucp and minor C-6 of (1→4)-ß-d-Galp. Small amounts of xylose and galactose exist in the forms of ß-d-Xylp-(1→ and ß-d-Gal-(1→. The immunomodulatory activity of DAP4 was measured on RAW 264.7 cells, the results proved that DAP4 exhibited excellent immunomodulatory activities, such as promoted the proliferation of spleen lymphocytes, increased NO production, as well as enhanced phagocytic of macrophages. Besides, DAP4 could also produce better enhancement on the vitality of NK cells. For the high immunomodulatory activity, DAP4 might be a potential source of immunomodulatory fucoidan with a novel structure.


Subject(s)
Phaeophyceae , Sulfates , Phaeophyceae/chemistry , Polysaccharides/chemistry , Sulfates/chemistry
11.
Mar Drugs ; 20(2)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35200621

ABSTRACT

Though the relationship between dietary fiber and physical health has been investigated widely, the use of dietary fiber from marine plants has been investigated relatively rarely. The Saccharina japonica byproducts after the production of algin contain a large amount of insoluble polysaccharide, which will cause a waste of resources if ignored. Soluble dietary fiber (SDF)prepared from waste byproducts of Saccharina japonica by alkaline hydrolysis method for the first time had a wrinkled microscopic surface and low crystallinity, which not only significantly reduced liver index, serum levels of aspartate aminotransferase (AST) and alanine amiotransferase (ALT), and liver fat accumulation damage to the livers of obese diabetic mice, but also activated the PI3K/AKT signaling pathway to increase liver glycogen synthesis and glycolysis. By LC-MS/MS employing a Nexera UPLC tandem QE high-resolution mass spectrometer, the 6 potential biomarker metabolites were screened, namely glycerophosphocholine (GPC), phosphocholine (PCho), pantothenic acid, glutathione (GSH), oxidized glutathione (GSSG), and betaine; several pathways of these metabolites were associated with lipid metabolism, glycogen metabolism, and amino acid metabolism in the liver were observed. This study further provided a detailed insight into the mechanisms of SDF from Saccharina japonica byproducts in regulating the livers of obese mice with type 2 diabetes and laid a reliable foundation for the further development and utilization of Saccharina japonica.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dietary Fiber/pharmacology , Laminaria/metabolism , Liver/drug effects , Animals , Chromatography, High Pressure Liquid , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/complications , Female , Liver/metabolism , Mice , Mice, Obese , Tandem Mass Spectrometry
12.
Mitochondrial DNA B Resour ; 6(4): 1303-1305, 2021 Mar 31.
Article in English | MEDLINE | ID: mdl-33855183

ABSTRACT

The complete mitochondrial genome of Sporobolus alterniflorus was a circular molecule of 566,328 bp in length and encoded 64 genes, including 35 protein-coding genes, 24 tRNA genes, and 5 rRNA genes. The most common initiated codon was ATG and the most common termination codon was CAT. The overall A + T content was 55.96%. The phylogenomic analysis revealed that Sporobolus alterniflorus have a closest phylogenetic relationship with Sorghum bicolor.

13.
Pak J Pharm Sci ; 34(6): 2197-2203, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35034881

ABSTRACT

Naproxen, known as the most potent non-steroid anti-inflammatory drugs, is vitally crucial in the treatment of neurodegenerative diseases. However, due to the poor brain penetration ability, it causes serious adverse effects with the therapeutic doses. Predictably, these unfavorable factors have hindered its further application. In this study, a novel brain-targeting conjugate, Nap-Pro, was designed and synthesized. The chemical stability and metabolic stability of this conjugate were determined in phosphate buffer, blood serum and brain homogenate, respectively. The cytotoxicity of Nap-Pro was evaluated in b End. 3 cells. In addition, the brain targeting capacity of Nap-Pro was also investigated in vivo. Importantly, Nap-Pro showed excellent capacity to cross the brain-blood barrier (BBB), suggesting probenecid was a super carrier that enhanced the delivery of drugs into brain. Collectively, the probenecid modification was a promising strategy to develop the novel drug delivery systems for brain targeting.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/metabolism , Brain/metabolism , Neuroprotective Agents/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Biological Transport , Blood-Brain Barrier/metabolism , Cell Line , Drug Compounding , Drug Stability , Mice , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/toxicity , Permeability , Tissue Distribution
14.
Mitochondrial DNA B Resour ; 5(3): 2516-2517, 2020 Jun 17.
Article in English | MEDLINE | ID: mdl-33457847

ABSTRACT

The complete mitochondrial genome of Pohlia nutans M211, sequenced using Illumina NovaSeq PE150, was 99864 bp in length. It encoded 65 genes, comprising 38 protein-coding genes, 24 tRNA genes and 3 ribosomal RNA genes. For these 38 PCGs, the most common start codon was ATG and the most common termination codon was TAA. The total GC content was 36.91% while the composition of A + T was 60.39%. Phylogenomic analysis indicated that P. nutans M211 was closely related to Mielichhoferia elongate.

15.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4786-4792, 2019 Nov.
Article in Chinese | MEDLINE | ID: mdl-31872583

ABSTRACT

The consistency of drug quality is related to the clinical efficacy and safety,which is highly valued by the government and relevant industries. Compared with chemical medicine,traditional Chinese medicine originates from the nature,and is greatly influenced by natural factors,such as the place of origin,cultivation and processing technology,climate. The quality consistency of traditional Chinese medicine is poor. The quality consistency has become the pain point and difficulty of the development of the traditional Chinese medicine industry,which seriously affects the stability and controllability of clinical efficacy and the reproducibility or recognition of modern research results. It is also a bottleneck for Chinese patent medicine to enter the international market. Mixed batch blending technology is an effective method for the scientific guarantee of the quality consistency in other industries and disciplines,and widely applied in liquor making industry,tobacco industry and perfume industry. Overseas,mixed batch blending technology has been successfully applied in guaranteeing the quality consistency of Ginkgo biloba preparations Jinnado. It has been used in the production of Chinese formulations in Japan for more than 30 years. In recent years,mixed batch blending technology has been introduced into the pharmaceutical field to ensure the quality consistency of traditional Chinese medicine,and relevant research has gradually increased.This manuscript reviews the application of blending technology in other disciplines,summarizes the algorithm principles and software systems of mixed batch blending in traditional Chinese medicine or natural medicine,explains the specific implementation process of mixed batch blending technology,and looks forward to the application prospects of artificial intelligence and other new technologies,in the hope of providing new ideas and technologies for breaking through the problem of quality consistency,and boosting the high-quality and high-level development of Chinese medicine industry in the new era.


Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Algorithms , Drug Industry , Reproducibility of Results , Technology
16.
Drug Deliv ; 19(7): 317-26, 2012.
Article in English | MEDLINE | ID: mdl-22985302

ABSTRACT

Chemotherapy in treatment of malignant tumors has many side effects due to the poor physiochemical properties and the toxicity to normal tissues. The dual-targeting drug delivery system combining two high-affinity ligands can target anticancer drug primary to the diseased tissue, then to the tumor, which provides both greater efficacy of treatment and less harm to normal tissues. In this paper, a novel dual-targeting moiety RGD(7) (R-G-D-D-D-D-D-D-D; Nonapeptide for bone cancer combining D(6) peptide as bone target moiety and RGD peptide as tumors target moiety was contracted. A series of bone and/or tumor targeting conjugates have been synthesized in a convergent approach and well characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The hydroxyapatite (HAP) binding, water solubility, the drug release and the distribution in vivo were evaluated. All the conjugates were water-soluble and able to release the parent drugs in vitro. The bone-targeting property of the dual-targeting delivery system was enhanced from the results of the HAP binding and the distribution in vivo. The experiment for verifying tumor targeting property was underway. These results provided an effective entry to the development of a new dual-targeting delivery system for bone cancer.


Subject(s)
Antineoplastic Agents/administration & dosage , Bone Neoplasms/drug therapy , Drug Delivery Systems , Fluorouracil/administration & dosage , Oligopeptides/administration & dosage , Animals , Durapatite/metabolism , Female , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oligopeptides/chemical synthesis , Prodrugs/chemical synthesis , Rats , Rats, Sprague-Dawley , Solubility , Tissue Distribution
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