RESUMO
Glioblastoma multiforme (GBM) exhibits a high mortality with an incidence rate of 3-5 per 100,000 each year, which demands existence of newer approach for its treatment. The current study focuses on synthesis of novel lipidic nanovesicles (LNs) loaded with highly potent macromolecule Lentinan (LNT) and surface modified with methoxy poly (ethylene glycol; PEG) amine (m-PEG-NH2)-grafted-chitosan (CS) for intranasal delivery. The grafting procedure was optimized using Box Behnken design (BBD) to limit the use of organic solvents. The fabricated polymer showed enhanced aqueous solubility, biodegradability and mucoadhesion, resulting in higher nasal mucosa permeation (z = 53.52 µm). The presence of PEG enabled the sustained release of LNT till 48 h and assisted in achieving higher accumulation of LNT in CSF (41.7 ± 3.1 µg/mL) and a higher brain targeting potential of 96.3 ± 2.31 % (p < 0.05). In-vitro cellular studies showed the enhanced anti-GBM effect of LNT on U87 MG cells by reducing the cell viability (~2 times reduction in IC50 value) accompanied with large number of cells undergoing late apoptosis and death (p < 0.05) because of the higher cellular uptake (63.22 ± 3.01 ng/100 cells) of novel formulation. The copolymer comprising LNs were biocompatible, stable and can be used as an effective tool in the management of GBM.
Assuntos
Administração Intranasal , Quitosana , Glioblastoma , Lentinano , Nanopartículas , Polietilenoglicóis , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Quitosana/química , Humanos , Lentinano/química , Lentinano/farmacologia , Lentinano/administração & dosagem , Polietilenoglicóis/química , Linhagem Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Animais , Ratos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Recently, lentinan (LNT) has been utilized for its diversified potential in research with an extended role from nutritional or medicinal applications to a novel biomaterial. LNT is a biocompatible, multifunctional polysaccharide employed as a pharmaceutical additive in engineering customized drug or gene carriers with an improved safety profile. Its triple helical structure containing hydrogen bonding offers more extraordinary binding sites for the attachments of dectin-1 receptors and polynucleotide sequences (poly(dA)). Hence, the diseases expressing dectin-1 receptors can be specifically targeted through so-designed LNT-engineered drug carriers. Gene delivery using poly(dA)-s-LNT complexes and composites has exhibited greater targetability and specificity. The achievement of such gene applications is assessed through the pH and redox potential of the extracellular cell membrane. The steric hindrance-acquiring behavior of LNT shows promise as a system stabilizer in drug carrier engineering. LNT shows viscoelastic gelling behavior temperature-dependently and therefore needs to explore more to meet topical disease applications. The immunomodulatory and vaccine adjuvant properties of LNT help in mitigating viral infections too. This review highlights the new role of LNT as a novel biomaterial, particularly in drug delivery and gene delivery applications. In addition, its importance in achieving various biomedical applications is also discussed.
Assuntos
Técnicas de Transferência de Genes , Lentinano , Lentinano/química , Terapia Genética , Portadores de FármacosRESUMO
The development of nanozymes with enhanced catalytic activity has been drawing great interest. Lentinan with special structure may be used to prepare bimetallic nanomaterials to enhance their catalytic activity. Herein, lentinan stabilized PdPt3 dendritic nanoparticles (PdPt3-LNT NDs) were prepared through reduction of Na2PdCl4 and K2PtCl4 with a molar ratio of 1:3 using lentinan as a biological template. PdPt3-LNT NDs had dendritic shape with size of 10.76 ± 1.82 nm. PdPt3-LNT NDs had the hydrodynamic size about 25.7 nm and the zeta potential between -1.4 mV and - 4.9 mV at different pH. Furthermore, PdPt3-LNT NDs catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) to produce oxidized TMB, suggesting their oxidase-like property. The catalytic activity of PdPt3-LNT NDs was the highest when pH was 4 and the temperature was 40 °C. The catalytic mechanism was the generation of reactive oxygen species- from O2 catalyzed by PdPt3-LNT NDs. More importantly, L-cysteine detection method was set up based on the oxidase-like property of PdPt3-LNT NDs. This method had wide linear range for 0-200 µM and low detection limit for 3.099 µM. Taken together, PdPt3-LNT NDs have good potential applications in bio-related detection in the future.
Assuntos
Lentinano , Nanopartículas , Cisteína , Lentinano/química , Oxirredutases , Espécies Reativas de OxigênioRESUMO
Postsurgical localized chemotherapy for breast cancer recurrence (BCR) still faces many problems which dampen researchers' enthusiasm and discounted prognosis. Simple strategies with controllable toxicities are expected to address these hurdles. Lentinan (LNT) has excellent biocompatibility and notable antitumor activity but rather low bioavailability after intravenous or oral administration. Here, a sponge-like LNT/chitosan composite (LNT/CS sponge) was prepared for efficient local delivery to prevent postoperative BCR. The obtained sponges exhibit uniform porosity and sustained release of LNT in vitro and in vivo. Furthermore, the sponges were implanted and showed significant reduction of postsurgical recurrence and suppression of long-term tumor regrowth with favorable biocompatibility in a subcutaneous postsurgical recurrence mouse model. Subsequent studies revealed that LNT can restrain the stemness of breast cancer cells, which may account for the long-term inhibition of tumor relapse. Therefore, LNT/CS sponge has a great potential as a promising alternative for postsurgical BCR.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quitosana , Lentinano/administração & dosagem , Cuidados Pós-Operatórios , Animais , Antineoplásicos/química , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Sobrevivência Celular , Quitosana/química , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Lentinano/química , Camundongos , Recidiva , Análise Espectral , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Biomedical implants-associated bacterial infections have become a major threat to human health. Therefore, it is meaningful to develop new antibacterial strategies to solve this problem. In this study, we conjugated acetylated lentinan (AceLNT) with α-terpineol (AceLNT-g-α-ter), a highly effective natural antibacterial compound, to constitute a novel AceLNT-g-α-ter membrane (AceLNT-g-α-terM). Compared with AceLNT membrane (AceLNTM), the adhesion amount of E. coli and P. aeruginosa in AceLNT-g-α-terM decreased by 80% and 85% after 7 d incubation in fluid bacterial medium. Moreover, the number of E. coli and P. aeruginosa biofilm on AceLNT-g-α-terM surface decreased by 70% and 71%. At the meanwhile, α-terpineol grafting modification of AceLNT had limited effect on its stimulating activity on macrophages and had no more cytotoxicity. In summary, our study firstly confirmed that AceLNT-g-α-terM could effectively inhibit gram-negative bacteria adhesion and biofilm formation, and provided a novel strategy for preventing infection of biomedical implants.
Assuntos
Antibacterianos/farmacologia , Monoterpenos Cicloexânicos/farmacologia , Escherichia coli/efeitos dos fármacos , Lentinano/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Acetilação , Animais , Antibacterianos/síntese química , Antibacterianos/química , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Monoterpenos Cicloexânicos/química , Citocinas/metabolismo , Lentinano/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Lentinan is a natural ß-glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug-drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib-lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib-lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug-drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.
Assuntos
Antineoplásicos/administração & dosagem , Lentinano/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Composição de Medicamentos , Células HCT116 , Células HEK293 , Humanos , Lentinano/química , Lentinano/farmacocinética , Simulação de Dinâmica Molecular , Nanopartículas , Tamanho da Partícula , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacocinética , Piridinas/química , Piridinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Solubilidade , SuspensõesRESUMO
Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.
Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos , Lentinano , Animais , Antineoplásicos/farmacocinética , Células Cultivadas , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Lentinano/análogos & derivados , Lentinano/síntese química , Lentinano/química , Lentinano/uso terapêutico , Masculino , Teste de Materiais , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Polimerização , Polímeros/síntese química , Polímeros/química , Polímeros/uso terapêutico , Porosidade , Coelhos , Dióxido de Silício/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lentinan, a ß-1,3-D-glucan, is clinically used as an immune enhancement drug for tumor therapy. Dectin-1 is a cell-surface immune receptor, which plays an important role in immunological defense against fungal pathogens and ß-glucan-mediated immune modulation. Herein we attempted to study the advanced structure of lentinan and how lentinan interacts with dectin-1 for its immune enhancement effect. We firstly used MD simulation and rigid macromolecule docking, combining some spectral techniques, to uncover the complex 3D conformation of a typical polysaccharide - lentinan, and the detailed interaction mode of lentinan with dectin-1. We proved by computational simulation that lentinan can maintain its triple-helix through hydrogen network and disclosed some structural properties of lentinan. We also characterized the affinity of lentinan to dectin-1 by LSPR and binding free energy calculation, and we found out that hydrogen bonds and CH-π interaction are the major contributors for lentinan's binding to dectin-1. Besides, after bound with lentinan, dectin-1 might surprisingly go through a conformational change. In summary, our work provided insights into lentinan's advanced structure and ß-glucan recognition by dectin-1.
Assuntos
Lectinas Tipo C/efeitos dos fármacos , Lentinano/farmacologia , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Análise por Conglomerados , Ligação de Hidrogênio , Proteínas Imobilizadas , Lectinas Tipo C/química , Lentinano/química , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação Proteica , Espectrometria de Fluorescência , Ressonância de Plasmônio de Superfície , ÁguaRESUMO
Herein the nucleic acid aptamers were attached to the polydeoxyadenylic acid (poly(dA)) tail for improving the tumor-targetability and cellular internalization of s-LNT/poly(dA) composite composed of two single chains of triple helical ß-glucan lentinan (s-LNT) and one poly(dA) chain. The in vitro results demonstrate that the cellular uptake of s-LNT/poly(dA) composites in MCF-7 cancer cells was enhanced effectively after attaching the aptamer. The as-prepared fluorescin isothiocyanate (FITC)-labelled LNT (LNT-FITC) through grafting was used for tracing the enhanced tumor-targetability of the composites. As a result, the cellular internalization of the LNT-FITC into MCF-7 and 4T1 cancer cells was further increased by the aptamer conjugated to poly(dA). Meanwhile, the in vivo experiments further demonstrate more s-LNT/poly(dA)-aptamer composites were effectively accumulated at the tumor site compared with s-LNT alone. This work provides a novel strategy for fabricating triplex ß-glucan as delivery vectors with active tumor-targetability.
Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/administração & dosagem , Lentinano/farmacologia , Neoplasias Mamárias Experimentais/terapia , Terapia de Alvo Molecular/métodos , Poli A/administração & dosagem , Animais , Antineoplásicos/química , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Linhagem Celular Tumoral , Portadores de Fármacos , Feminino , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Humanos , Injeções Intravenosas , Lentinano/química , Células MCF-7 , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Poli A/química , Poli A/genética , Coloração e Rotulagem/métodosRESUMO
Graphene oxide (GO) and lentinan have received great attention because of their utility in biomedical applications. Graphene oxide is utilized in drug- and vaccine-delivery systems due to its biocompatibility, large surface area, and outstanding adsorption capability, while lentinan has immunity-enhancing effects. In this study, we synthesized and characterized GO grafted with lentinan (LNT) as an adjuvant and investigated how to impact the immune responses. Lentinan-modified GO (GO-LNT) facilitated antigen uptake in macrophages and improved the efficiency of antigen application in vitro. Furthermore, in vivo, compared with GO/OVA, GO-LNT/OVA decreased the release rate of ovalbumin (OVA) to sustain long-term immune responses and boost the levels of IgG and IgG subtypes. Hence, we can infer that the effects of GO-LNT were a result of the increased amounts of antigen uptake by cells. Overall, our studies demonstrated that GO-LNT could suffice for a safe and effective vaccine-delivery system as well as an excellent adjuvant that both elicits a long-term immune memory response and potentiates cellular and humoral immunity.
Assuntos
Imunidade Adaptativa , Portadores de Fármacos/química , Grafite/química , Imunidade Inata , Lentinano/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Feminino , Corantes Fluorescentes/química , Imunoglobulina G/sangue , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Imagem Óptica , Ovalbumina/química , Ovalbumina/imunologia , Ovalbumina/metabolismoRESUMO
Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.
Assuntos
GTP Fosfo-Hidrolases/metabolismo , Lentinano/farmacologia , Mitocôndrias/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Nanopartículas/química , Selênio/farmacologia , Fator 3 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Feminino , Humanos , Lentinano/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Effects of a novel slit divergent ultrasound (SDU) treatment on soybean protein isolate (SPI)-lentinan conjugates via Maillard reaction was investigated. Besides, the stability of emulsions prepared by SPI and SPI-lentinan conjugates (ultrasound and un-ultrasound) as emulsifiers was compared. The results showed that ultrasonic treatment (40 min) markedly increased the degree of grafting (26.48%) by 1.91 times comparing with traditional heating method (2 h, 13.89%). In addition, structural analysis showed that the conjugates obtained by SDU treatment changed the secondary structure and had higher surface hydrophobicity and fluorescence intensity than those obtained by traditional heating method. Apart from this, SDU treatment could significantly improve the functional properties (solubility, foaming, emulsifying capacity, thermal stability, and viscosity) of conjugates. Furthermore, the emulsions prepared by the SPI-lentinan conjugates (ultrasound) as emulsifiers possessed the highest stability against environmental stresses. Taken together, SDU-assisted heating could be an excellent method to improve the functional properties of conjugates.
Assuntos
Emulsões/química , Lentinano/química , Reação de Maillard , Proteínas de Soja/química , Dicroísmo Circular , Emulsificantes/química , Fluorescência , Indústria de Processamento de Alimentos/métodos , Glicosilação , Calefação , Interações Hidrofóbicas e Hidrofílicas , Estabilidade Proteica , Estrutura Secundária de Proteína , Solubilidade , Proteínas de Soja/isolamento & purificação , Ultrassom , Viscosidade , Água/químicaRESUMO
Cancer is a leading cause of human mortality. Given that it is difficult for conventional therapeutic approaches to effectively eradicate tumors and inhibit their recurrence and metastasis, new therapeutic strategies for solving this problem are urgently needed. In this work, we report the development of a two-dimensional titanium carbide nanocomposite drug delivery system. The system can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system. A surface modification engineering strategy has been elaborately designed to realize the multifunctionalization of an MXene, Ti3C2. In this strategy, the nanocomposite drug delivery system (Ti3C2@Met@CP) was established via layer by layer adsorption of metformin (Met) and compound polysaccharide (CP) on the surface of Ti3C2 nanosheets. Among these materials, the synthesized (AlOH)4--functionalized Ti3C2 nanosheets possess strong near-infrared absorption (extinction coefficient of 36.2 L g-1 cm-1), high photothermal conversion efficiency (â¼59.6%) and effective singlet oxygen generation (1O2). Compound polysaccharide (CP) is a new immunomodulator formed by mixing lentinan, pachymaran and tremella polysaccharides in optimal proportions. Especially, the decoration of CP onto the Ti3C2 nanosheets endows Ti3C2 with a well-defined shell, improves its tumor site aggregation and biocompatibility, and activates the host's immune functions. The synergistic eradication and inhibition of tumor recurrence and metastasis have been systematically evaluated by in vivo and in vitro experiments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Nanocápsulas/química , Nanocompostos/química , Titânio/química , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Materiais Biocompatíveis/química , Terapia Combinada , Liberação Controlada de Fármacos , Feminino , Glucanos/química , Glucanos/farmacologia , Humanos , Raios Infravermelhos , Lentinano/química , Lentinano/farmacologia , Metformina/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Fototerapia , Polissacarídeos/química , Oxigênio Singlete/químicaRESUMO
Lentinan is widely used as a therapeutic agent for treatment of malignant tumors in clinical practice. The chemical structure of lentinan is highly associated with its biological activity. In this study, the correlation between the structure of lentinan and its immune activity was investigated to assess the function of key parameters that can influence quality control of lentinan. The results showed that the batch-to-batch consistency of two lentinan samples was satisfactory, indicating the stability of production process of lentinan. However, although the chemical composition and triple-helical conformation (THC) of the tested samples were relatively similar, their Mw, polydispersity index (PDI), and Rgz remarkably varied due to different production processes. In vitro immunomodulatory assay reflects that lentinan could stimulate the macrophages phagocytic capacity. Meanwhile, lentinan samples could improve the spleen and thymus indices, promote the proliferation of lymphocytes and adjust for the percentages of CD4+ and CD8+ T cells in vivo. Furthermore, the immunomodulatory effect of lentinan sample B (Mw: 650,700 g/mol) was superior than that of the sample A (Mw: 4,818,700 g/mol). It was noted that the Mw should be detected as a necessary index for quality control of lentinan to ensure stability and effectiveness of the production process.
Assuntos
Lentinano/normas , Adjuvantes Imunológicos/normas , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Lentinano/química , Lentinano/imunologia , Lentinano/toxicidade , Camundongos , Fagocitose/efeitos dos fármacos , Controle de Qualidade , Células RAW 264.7RESUMO
Improving plant resistance against systemic diseases remains a challenging research topic. In this study, we developed a dual-action pesticide-loaded hydrogel with the capacity to significantly induce plant resistance against tobacco mosaic virus (TMV) infection and promote plant growth. We produced an alginate-lentinan-amino-oligosaccharide hydrogel (ALA-hydrogel) by coating the surface of an alginate-lentinan drug-loaded hydrogel (AL-hydrogel) with amino-oligosaccharide using electrostatic action. We determined the formation of the amino-oligosaccharide film using various approaches, including Fourier transform infrared spectrometry, the ζ potential test, scanning electron microscopy, and elemental analysis. It was found that the ALA-hydrogel exhibited stable sustained-release activity, and the release time was significantly longer than that of the AL-hydrogel. In addition, we demonstrated that the ALA-hydrogel was able to continuously and strongly induce plant resistance against TMV and increase the release of calcium ions to promote Nicotiana benthamiana growth. Meanwhile, the ALA-hydrogel maintained an extremely high safety to organisms. Our findings provide an alternative to the traditional approach of applying pesticide for controlling plant viral diseases. In the future, this hydrogel with the simple synthesis method, green synthetic materials, and its efficiency in the induction of plant resistance will attract increasing attention and have good potential to be employed in plant protection and agricultural production.
Assuntos
Antivirais/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Lentinano/química , Lentinano/farmacologia , Nicotiana/virologia , Doenças das Plantas/virologia , Vírus do Mosaico do Tabaco/fisiologia , Alginatos/química , Antivirais/farmacologia , Preparações de Ação Retardada/química , Resistência à Doença , Hidrogéis/química , Doenças das Plantas/imunologia , Nicotiana/imunologiaRESUMO
Development of high photothermal performance and biocompatible nanotherapeutic agents is of great importance for photothermal cancer treatment. In this paper, we have developed lentinan decorated tungsten oxide nanorods (W18O49@LTN NRs) via a mild one-step solvothermal route. Owing to the numerous surface hydroxyl groups of polymer chains, the presence of lentinan layer in the surface of W18O49 NRs lead to good biocompatibility. The lentinan layer also affects the crystal structure of W18O49 and improves near-infrared absorption (~1.7â¯×â¯109â¯M-1â¯cm-1 at 980â¯nm), which is two orders of higher than previously reported PEGylated W18O49 nanowires. Even under near-infrared (NIR) laser irradiation at a very low power density of 0.4â¯W/cm2, the temperature of W18O49@LTN NRs aqueous dispersion (125⯵g/mL) could increase by 15.1⯰C. The photothermal conversion efficiency of W18O49@LTN NRs reaches 33.86%, which is higher than previously reported WO3-x hierarchical nanostructures (28.1%). Importantly, when cancer cells were treated with W18O49@LTN NRs (200⯵g/mL) and 980â¯nm laser (0.4â¯W/cm2), a significant photo-induced cell killing behavior was observed. This work demonstrates that W18O49@LTN NRs have the potential for precise cancer treatment.
Assuntos
Lentinano/química , Lentinano/uso terapêutico , Nanomedicina/métodos , Nanotubos/química , Neoplasias/terapia , Óxidos/química , Fototerapia/métodos , Tungstênio/químicaRESUMO
Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. ß-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways. Though it has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since 1980s, a systematic review of clinical studies of lentinan has not been conducted elaborately. In this review, over 9474 reported lentinan-associated cancer treatment cases are evaluated and summarized from 135 independent studies in China during the past 12 years (2004-2016) based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database. The 9474 reported lentinan-associated cancer treatment cases include lung cancer (3469 cases), gastric cancer (3039 cases), colorectal cancer (1646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), Non-Hodgkin lymphoma (70 cases), pancreatic cancer (15 cases), cardiac cancer (15 cases), nasopharyngeal cancer (14 cases), duodenal cancer (1 case) and 110 cancer cases with no classifying patient information. Overall clinical data show solid effect of lentinan on improving the quality of life and on promoting the efficacy of chemotherapy and radiation therapy during cancer treatment.
Assuntos
Agaricales/química , Lentinano/uso terapêutico , Neoplasias/tratamento farmacológico , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/química , Adjuvantes Farmacêuticos/uso terapêutico , China , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/uso terapêutico , Lentinano/efeitos adversos , Lentinano/químicaRESUMO
Immuno-therapies are gaining more importance to treat certain forms of cancer. The goal of therapies is to enhance person's own IgG, IgA, IgM, IgD, IgE and macrophages to combat with neoplastic cells hence the effectiveness of the immune system. Since, early civilization mushrooms are considered as potent food as well as medicine. Mushrooms are well known for their bioactive compounds such as chizophyllan, lentinan, grifolan, PSP (polysaccharide-peptide complex) and PSK (polysaccharide-protein complex) which are considered as medicines against melignancy. They prevent oncogenesis by the direct effect on tumor metastasis and exhibits antitumor effects by the induction of immune response in host. Mushroom polysaccharides have promising future for treatment of cancers due to their mode of action and efficacy. Also there are some hurdles during this treatment, but it will start a new era of safer and effective medicine based on mushroom polysaccharides.
Assuntos
Agaricales/química , Antineoplásicos/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Lentinano/química , Lentinano/farmacologia , Neoplasias/tratamento farmacológico , Polissacarídeos/efeitos adversos , Proteoglicanas/química , Proteoglicanas/farmacologia , beta-Glucanas/química , beta-Glucanas/farmacologiaRESUMO
A lentinan (LEN) functionalized multi-walled carbon nanotubes (MWCNTs) drug delivery system, using tamoxifen (TAM) as a model anticancer agent, was developed by a simple non-covalent approach. This developed system (MWCNTs-TAM-LEN) possessed good stability, water dispersibility and extraordinary photothermal properties. It was demonstrated by the in vitro experiments that MWCNTs-TAM-LEN had enhanced cellular uptake, antitumor activity and cell apoptosis on Mcf-7 cells in comparison with TAM and MWCNTs-TAM. The cell inhibition rate and apoptosis rate of Mcf-7 cells treated by MWCNTs-TAM-LEN with near-infrared (NIR) were 67.1% and 66.5% higher than that of equivalent concentration of TAM with NIR irradiation treatment, respectively. The enhanced antitumor efficacy of MWCNTs-TAM-LEN was realized via the synergistic function of chemotherapy and photothermal ablation under NIR laser irradiation.
Assuntos
Técnicas de Ablação , Portadores de Fármacos/química , Lentinano/química , Nanotubos de Carbono/química , Tamoxifeno/química , Tamoxifeno/farmacologia , Transporte Biológico , Terapia Combinada , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Tamoxifeno/metabolismo , Tamoxifeno/uso terapêuticoRESUMO
Misfolding and aggregation of human islet amyloid polypeptide (hIAPP) into fibrils are important contributions to the pathology of type 2 diabetes. Developing effective inhibitors of protein aggregation and fibrillation has been considered a promising therapeutic approach to preventing and treating type 2 diabetes. Herein, we report that Shiitake-derived polysaccharide lentinan manipulates in vitro hIAPP fibrillation and modulates IAPP-induced cytotoxicity in a conformation-dependent manner. In its triple-helical conformation, lentinan effectively inhibits hIAPP fibrillation, either in bulk solution or in the presence of lipid membrane, suppresses reactive oxygen species (ROS) generation, and attenuates hIAPP-induced cell toxicity. In contrast, lentinan accelerates hIAPP aggregation when it exists in a random-coil conformation and shows no suppression on hIAPP-mediated ROS production. Further investigation shows that the interaction between triple-helical lentinan and monomeric hIAPP is more favorable than the intermolecular binding of hIAPP, which redirects hIAPP aggregates to discrete nontoxic nanocomposites. To the best of our knowledge, this is the first time to report a conformation-dependent inhibition of hIAPP aggregation, which will provide new insights for our understanding of the manipulation mechanisms on hIAPP by natural polysaccharides and open a new avenue for designing and screening potential amyloid inhibitors against type 2 diabetes.