RESUMEN
Immobilized enzymes are one of the most common tools used in enzyme engineering, as they can substantially reduce the cost of enzyme isolation and use. However, efficient catalysis of solid substrates using immobilized enzymes is challenging, hydrolysis of insoluble cellulose by immobilized cellulases is a typical example of this problem. In this study, inspired by bees and honeycombs, we prepared gelatin-modified cellulase (BEE) and gelatin hydrogels (HONEYCOMB) to achieve reversible recycling versus release of cellulase through temperature-responsive changes in the triple-stranded helix-like interactions between BEE and HONEYCOMB. At elevated temperatures, BEE was released from HONEYCOMB and participated in hydrolytic saccharification. After 24 h, the glucose yields of both the free enzyme and BEE reached the same level. When the temperature was decreased, BEE recombined with HONEYCOMB to facilitate the effective separation and recycling of BEE from the system. The enzymatic system retained >70 % activity after four reuse cycles. In addition, this system showed good biocompatibility and environmental safety. This method increases the mass transfer capacity and enables easy recovery of immobilized cellulase, thereby serving as a valuable strategy for the immobilization of other enzymes.
Asunto(s)
Celulasa , Celulosa , Enzimas Inmovilizadas , Gelatina , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Hidrólisis , Celulasa/química , Celulasa/metabolismo , Celulosa/química , Gelatina/química , Temperatura , Hidrogeles/química , Solubilidad , AnimalesRESUMEN
To control hypertension, long-term continuous antihypertensive therapeutics are required and five classes of antihypertensive drugs are frequently involved, including diuretics, ß-blockers, calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors. Although with demonstrated clinical utility, there is still room for the improvement of many antihypertensive drugs in oral tablet or capsule dosage form, in terms of reducing systemic side effects and first-pass hepatic drug uptake. Meanwhile, nanocarrier-mediated transdermal drug delivery systems have emerged as a powerful tool for various disease treatments. With benefits such as promoting patient compliance for long-time administration, enhancing skin permeability, and reducing systemic side effects, these systems are reasonably investigated and developed for the transdermal delivery of multiple antihypertensive drugs. This review aims to summarize the literature relating to nanosystem-based transdermal antihypertensive drug delivery and update recent advances in this field, as well as briefly discuss the challenges and prospects of engineering transdermal delivery nanosystems for hypertension treatment.
Asunto(s)
Antihipertensivos , Hipertensión , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio , Administración Cutánea , Antagonistas Adrenérgicos beta/uso terapéuticoRESUMEN
Pharmaceutical peptide Octreotide is a somatostatin analog with targeting and therapeutic abilities. Over the last decades, Octreotide has been developed and approved to treat acromegaly and neuroendocrine tumours, and Octreotide-based radioactive conjugates have been leveraged clinically to detect small neuroendocrine tumour sites. Meanwhile, variety of Octreotide-derived delivery strategies have been proposed and explored for tumour targeted therapeutics or diagnostics in preclinical or clinical settings. In this review, we especially focus on the preclinical development and applications of Octreotide-derived drug delivery systems, diagnostic nanosystems, therapeutic nanosystems and multifunctional nanosystems, we also briefly discuss challenges and prospects of these Octreotide-derived delivery systems.
RESUMEN
Habitat use and the temporal activities of wildlife can be largely modified by livestock encroachment. Therefore, identifying the potential impacts of livestock on the predator-prey interactions could provide essential information for wildlife conservation and management. From May to October 2017, we used camera trapping technology to investigate fine-scale spatiotemporal interactions in a predator-prey system with the leopard cat (Prionailurus bengalensis) as a common mesopredator, and its prey with contrasting activity patterns (i.e., nocturnal rats and diurnal squirrels) in a livestock-dominated nature reserve in Northern China. We found that the prey species showed different habitat preferences with the leopard cats. The nocturnal rats had strong positive effects on the site-use of the leopard cats, while the influence of livestock on the diurnal squirrels' site-use changed from strong positive effects to weak effects as the livestock disturbance increased. The temporal overlap between the leopard cats and the nocturnal rats was almost four times that of the leopard cats and the diurnal squirrels, regardless of the livestock disturbance. Our study demonstrated that the fine-scale spatiotemporal use patterns of the leopard cats were consistent and highly correlated with the nocturnal rats under livestock disturbance. We suggest that appropriate restrictions on livestock disturbance should be implemented by reserve managers to reduce the threat to wildlife and achieve multi-species coexistence.
RESUMEN
Immobilizing cellulase for improving its hydrolysis activity and recyclability is critical for a cost-effective and environment-friendly conversion of cellulosic biomass. However, developing a strategy for achieving a high mass-transfer rate and good separation efficiency between an insoluble cellulose substrate and cellulase remains difficult. Instead of the traditional method, a single-enzyme molecular modification method is used in this study. To modify cellulase and provide it with a temperature-pH dual responsive property, systemized poly(acrylic-acrylonitrile) (PAA-PAN) molecular arms are used. The modified cellulase can reversibly transform between liquid and solid phases. In the liquid phase, the modified cellulase can adjust its active center, increasing its hydrolysis efficiency and separation efficiency. Cellulase and glucose products can be easily separated in the solid phase, allowing the reuse of cellulase. The results show that the modified cellulase's hydrolysis efficiency is comparable to that of free cellulase and that the modified enzyme preserves more than 60% of its initial activity after 15 batches of efficient hydrolysis. Thus, the proposed modification route considerably lowers the cost of cellulose enzymatic hydrolysis.
Asunto(s)
Celulasa , Celulosa , Celulasa/química , Celulosa/química , Glucosa/química , Hidrólisis , TemperaturaRESUMEN
We studied the influence of Lactobacillus reuteri SL001 (L. reuteri SL001) on the gut microbial community in Alzheimer's disease model mice (APP/PS1 double transgenic mice, ADmice) and wild type (C57BL/6) mice. The AD model mice and wild type mice were divided into test and control groups (4 in total), with 5 mice each and only male mice. The test group was fed with 0.2 mL suspension of L. reuteri SL001 at 5×10¹¹ CFU/mL. The control group received the same amount of sterile PBS daily for 45 days. Fecal samples were collected to compare and analyze the community structure and diversity of microbiota through high-throughput sequencing of the V3-V4 region of 16S rRNA gene. By sequence alignment and classification, the intestinal microbial OTUs of the 4 groups including 19 phyla, 40 classes, 64 orders, 104 families and 175 genera. The α diversity of AD model mice was greater than that of wild type mice, but the difference between the two was small. After adding L. reuteri SL001, the α diversity of both mice increased, and the increase in AD model mice was smaller. At the phyla level, the dominant phyla of the four groups of mice were Bacteroidetes, Firmicutes and Proteobacteria. The abundance of Bacteroides phylum in AD model mice was lower than that of wild type, and the abundance of chlamydomonas was higher than that of wild type. Feeding L. reuteri SL001 reduced the proportion of Firmicutes/Bacteroidetes (F/B) in mice. At the order level, the relative abundance of Bacteroidales, Lactobacillales, Bacillales and Bifidobacteriales in AD model mice was lower than that of wild type mice. At the genus level, the abundant genera were Allobaculum, Lachnospiraceae_NK4A136_group, Bacteroides and Lactobacillus. The relative abundance of Bacteroides, Lactobacillus, Bifidobacterium and Alloprevotella in AD model mice was lower than that in wild type mice. Adding L. reuteri SL001 increased the abundance of these genera and Bacteroides, Lactobacillus, Bacillus and Bifidobacteria in AD model mice. The relative abundance of Butyrivibrio in AD model mice was also lower than that in wild type, but after the feeding of L. reuteri SL001, the relative abundance was reduced in both mice. The dominant strains of wild-type mice were Lactobacillus, and no dominant flora was found in AD model mice. The results in this article provide valuable data for revealing the difference in intestinal microbial diversity between AD model mice and C57BL/6 mice, and feeding L. reuteri SL001 play positive roles in adjusting the intestinal bacterial community structure of AD model mice.
Asunto(s)
Microbioma Gastrointestinal , Limosilactobacillus reuteri , Animales , Lactobacillus , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genéticaRESUMEN
Core-shell nanoparticles have grown in popularity in the past few years due to their versatile features and multiple biomedical applications as drug delivery systems. In order to improve bioavailability and reduce adverse effects, the biomimetic concept has been integrated into core-shell architectural designs. In this regard, the 'camouflage' shell comprised of various cellular membranes renders these nanoparticles a multifunctional platform that combines the merits of native cellular membranes with the advantages of biomaterials. Since leukocytes have a specific tropism for inflammatory or tumour sites and can infiltrate into these lesions, the marriage of leukocyte cell membrane shell with functional nanoparticle core is expected to achieve long time circulation, targeted delivery and improved ability of overcoming certain physiological barriers. In this review, we focus mainly on the recent development of nanoparticles cloaked with the leukocyte membrane and their applications in different biomedical fields of interest, including cancer therapy, inflammatory regulation and immune modulation. Additionally, current challenges and future prospects of leukocyte membrane coated core-shell nanoparticles are also briefly discussed.
Asunto(s)
Membrana Celular/metabolismo , Leucocitos/citología , Nanopartículas/química , Animales , Enfermedades Autoinmunes/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Humanos , Inflamación/tratamiento farmacológico , Leucocitos/metabolismo , Macrófagos/metabolismo , Monocitos/metabolismo , Neoplasias/tratamiento farmacológicoRESUMEN
Reflux precipitation polymerization (RPP) represents an effective approach that enables to prepare various types of polymeric nanogels with precise control over the morphology and structure. Owing to facile loading or modification by a variety of functional moieties, rationally designed nanogels pose the possibility to attain a platform for tailoring functional properties that could be widely used for various biomedical applications, such as multifunctional drug delivery, enrichment of functional peptides, separation of specific proteins, as well as detection of circulating tumor cells. This feature article highlights RPP as a promising polymerization strategy that provides access to facile generation of modular nanostructures or multifunctional properties in a diverse range of biomedical applications, proving that RPP has great potential to become one of the most attractive polymerization techniques in polymer chemistry.
Asunto(s)
Materiales Biocompatibles/química , Geles/química , Nanoestructuras/química , Polimerizacion , Sistemas de Liberación de MedicamentosRESUMEN
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of GPC3+ HCC cells to this engineered cell line resulted in significant in vitro cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-ß did not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no significant difference in anti-tumor activities was observed in hypoxic (1%) conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in multiple HCC xenografts with both high and low GPC3 expression, but not in those without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC xenografts. Similarly, efficient retargeting on primary NK cells was achieved. These results justified clinical translation of this GPC3-specific, NK cell-based therapeutic as a novel treatment option for patients with GPC3+ HCC.
Asunto(s)
Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Glipicanos/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Receptores Quiméricos de Antígenos/metabolismo , Animales , Línea Celular Tumoral , Citocinas/metabolismo , Epítopos , Expresión Génica , Orden Génico , Vectores Genéticos/genética , Glipicanos/genética , Xenoinjertos , Humanos , Inmunofenotipificación , Inmunoterapia Adoptiva , Lentivirus/genética , Ratones , Fenotipo , Receptores Quiméricos de Antígenos/genética , Transducción GenéticaAsunto(s)
Antineoplásicos Inmunológicos/farmacología , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/tratamiento farmacológico , Antineoplásicos Inmunológicos/inmunología , Línea Celular Tumoral , Proteínas Ligadas a GPI/inmunología , Humanos , Mesotelina , Proteínas de Neoplasias/inmunología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patologíaRESUMEN
Development of rational vectors for efficient drug and gene delivery is crucial for cancer treatment. In this study, epidermal growth factor receptor (EGFR)-binding peptide amphiphile (PA) were used as the primary bilayer skeleton material to construct ultra-stable self-assembling peptide nanovesicle (SPV). The resulted EGFR-targeted SPV (ESPV) could efficiently encapsulate therapeutic cargos (drugs or small interfering RNAs [siRNAs]) or labelled fluorescent cargo (quantum dots [QDs]) and exhibited excellent affinity for EGFR-positive cancer cells. Moreover, ESPV could deliver more drug or plasmid DNA to tumour sites and promote gene expression (a three-fold ratio of ESPVs vs cationic liposomes). Notably, the individual delivery or co-delivery of doxorubicin (DOX) and the acetylcholinesterase (AChE) gene via the ESPVs resulted in excellent drug/gene delivery both in vitro and in vivo and exerted a significant growth-suppressing effect on a liver cancer xenograft. This nanoscale, targeted cargo-packaging technology may provide a new strategy for the design of highly targeted cancer therapy vectors.
Asunto(s)
Receptores ErbB/metabolismo , Terapia Genética/métodos , Nanocápsulas/química , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/terapia , Péptidos/farmacocinética , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Terapia Molecular Dirigida/métodos , Nanocápsulas/ultraestructura , Neoplasias Experimentales/genética , Péptidos/química , Transfección/métodos , Resultado del TratamientoRESUMEN
Specific targeting of tumor cells to achieve higher drug levels in tumor tissue and to overcome side effects is the major goal in cancer chemotherapy. In this study, we used a tumor targeting peptide, GE11, to conjugate onto the surface of doxorubicin encapsulated phospholipid micelles. The GE11 peptide triggered specific binding to epidermal growth factor receptor (EGFR), leading to enhanced cellular uptake and cytotoxicity in vitro and highly accumulation in the tumors in vivo. The results indicated that GE11 conjugated phospholipid micelles should have potential applications in cancer therapy.
Asunto(s)
Doxorrubicina/administración & dosificación , Receptores ErbB/metabolismo , Fosfolípidos/administración & dosificación , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Micelas , Péptidos/metabolismoRESUMEN
Self-assembly of anticancer small molecules into nanostructures may represent an attractive approach to improve the treatment of experimental solid tumors. As a proof of concept, we designed and synthesized the conjugate prodrug of hydrophilic gemcitabine by its covalent coupling to hydrophobic chlorambucil via a hydrolyzable ester linkage. The resulting amphiphilic conjugates self-assembled into nanoparticles in water and exhibited significant anticancer activity in vitro against a variety of human cancer cells. In vivo anticancer activity of these nanoparticles has been tested on subcutaneous grafted SMMC-7721 hepatocellular carcinoma model. Such chlorambucil gemcitabine conjugate nanomedicine should have potential applications in cancer therapy.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Clorambucilo/administración & dosificación , Desoxicitidina/análogos & derivados , Nanoconjugados/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Clorambucilo/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Nanoconjugados/administración & dosificación , Nanomedicina/métodos , Trasplante de Neoplasias , GemcitabinaRESUMEN
The nonspecific toxicity of anticancer drug doxorubicin (DOX) toward both tumor and normal cells can result in serious side effects, thereby limiting its clinical applications. In this wok, epidermal growth factor receptor (EGFR) antagonist peptide GE11 was introduced into DOX structure via a disulfide bond which can be cleaved by reduced glutathione (GSH). We have investigated the intracellular delivery and in vitro cytotoxicity of GE11-DOX conjugate and free DOX in high (SMMC-7721) and low (MCF-7) EGFR expressing cancer cell models. GE11-DOX accumulated at higher levels in SMMC-7721 cells than in MCF-7 cells, while the cellular uptake of free DOX was almost the same in both cells. Furthermore, pretreating with anti-EGFR monoclonal antibody reduced intracellular accumulation of GE11-DOX in SMMC-7721, indicating the involvement of EGFR pathway in the transport of conjugate. Our results suggest that GE11-DOX conjugate has the potential to be a therapeutic agent for treating EGFR overexpressing tumor.
Asunto(s)
Antibióticos Antineoplásicos/metabolismo , Doxorrubicina/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Diseño de Fármacos , Receptores ErbB/metabolismo , Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Receptores ErbB/antagonistas & inhibidores , Humanos , Células MCF-7RESUMEN
An active heterogeneous catalyst, namely 1,1,3,3-tetramethylguanidine (TMG) immobilized on mesoporous SBA-15 silica (SBA-15-pr-TMG), was prepared and the catalytic activity was investigated for transesterification of soybean oil with methanol. The heterogeneous catalysts were characterized using Hammett titration method, Fourier transform infrared spectra, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, and X-ray photoelectron spectroscopy techniques. It is shown that the activity of the catalysts for the transesterification reaction is closely related to their basic properties. By using this catalyst, an environmentally benign process for biodiesel production in a heterogeneous manner was developed. When the reaction was carried out at reflux of methanol, with a molar ratio of methanol to soybean oil of 15:1, a reaction time 12h and a catalyst amount 5 wt%, the oil conversion of 91.7% was achieved. The catalyst could be recovered easily and reused without significant degradation in activity.
Asunto(s)
Guanidinas/química , Dióxido de Silicio/química , Aceite de Soja/química , Catálisis , Esterificación , PorosidadRESUMEN
In the crystal structure of the title compound, C(19)H(17)FN(4)O(2)S, mol-ecules are linked via pairs of N-Hâ¯N inter-actions, forming centrosymmetric dimers. Two intra-molecular N-Hâ¯O hydrogen bonds stabilize the mol-ecular conformation.