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Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.
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Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Micro-Ondas , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológicoRESUMO
Nano-engineering with unique "custom function" capability has shown great potential in solving technical difficulties of nanomaterials in tumor treatment. Through tuning the size and surface properties controllablly, nanoparticles can be endoewd with tailored structure, and then the characteristic functions to improve the therapeutic effect of nanomedicines. Based on nano-engineering, many have been carried out to advance nano-engineering nanomedicine. In this review, the main research related to cancer therapy attached to the development of nanoengineering nanomedicines has been presented as follows. Firstly, therapeutic agents that target to tumor area can exert the therapeutic effect effectively. Secondly, drug resistance of tumor cells can be overcome to enhance the efficacy. Thirdly, remodeling the immunosuppressive microenvironment makes the therapeutic agents work with the autoimmune system to eliminate the primary tumor and then prevent tumor recurrence and metastasis. Finally, the development prospects of nano-engineering nanomedicine are also outlined.
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Nanopartículas , Neoplasias , Humanos , Nanomedicina , Neoplasias/terapia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Imunossupressores/farmacologia , Microambiente TumoralRESUMO
Gadolinium-doped carbon dots (Gd-CDs), as a new class of nanomaterial, has a wide application prospect in targeted imaging and monitoring diagnosis and treatment of liver cancer because of their good fluorescence (FL)-magnetic resonance (MR) imaging properties. First, Gd-CDs were synthesized by hydrothermal method with gadodiamide as gadolinium source, citric acid as carbon source and silane coupling agent (KH-792) as coupling agent with FL quantum yield (QY) of 48.2%. Then, folic acid (FA), which is highly expressed in liver cancer, was used as a targeting component to modify Gd-CDs to obtain targeted imaging agent (Gd-CDs-FA). The results showed that Gd-CDs and Gd-CDs-FA have low cytotoxicity and good biocompatibility, and the targeting and selectivity of Gd-CDs-FA to HepG2 cells could be observed under confocal laser scanning microscope (CLSM). The T1 longitudinal relaxation rates (r1) of Gd-CDs and Gd-CDs-FA are 15.92 mM-1s-1 and 13.56 mM-1s-1, respectively. They showed good MR imaging ability in vitro and in vivo, and MR imaging in nude mice further proved the targeting imaging performance of Gd-CDs-FA. Therefore, Gd-CDs-FA with higher QY showed good FL-MR targeting imaging ability of liver cancer, which broke through the limitations of single molecular imaging probe in sensitivity and soft tissue resolution. This study provides a new idea for the application of Gd-CDs in FL and MR targeting imaging of liver cancer.
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Neoplasias Hepáticas , Pontos Quânticos , Animais , Camundongos , Meios de Contraste , Fluorescência , Gadolínio , Carbono , Ácido Fólico , Camundongos Nus , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.
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Infecções por Coronavirus , Crataegus , Vírus da Diarreia Epidêmica Suína , Quercetina/análogos & derivados , Doenças dos Suínos , Animais , Suínos , Diarreia , Antivirais/farmacologia , Antivirais/uso terapêutico , Doenças dos Suínos/tratamento farmacológicoRESUMO
Limited information on the virome and bacterial community hampers our ability to discern systemic ecological risk factors that cause cattle diarrhea, which has become a pressing issue in the control of disease. A total of 110 viruses, 1,011 bacterial genera, and 322 complete viral genomes were identified from 70 sequencing samples mixed with 1,120 fecal samples from 58 farms in northeast China. For the diarrheic samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, and geographic distribution in relation to different disease-associated ecological factors; the abundance of identified viruses and bacteria was significantly correlated with the host factors of clinical status, cattle type, and age, and with environmental factors such as aquaculture model and geographical location (P < 0.05); a significant interaction occurred between viruses and viruses, bacteria and bacteria, as well as between bacteria and viruses (P < 0.05). The abundance of SMB53, Butyrivibrio, Facklamia, Trichococcus, and Turicibacter was significantly correlated with the health status of cattle (P < 0.05). The proportion of BRV, BCoV, BKV, BToV, BoNoV, BoNeV, BoAstV, BEV, BoPV, and BVDV in 1,120 fecal samples varied from 1.61% to 12.05%. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. A genome-based phylogenetic analysis revealed high variability of 10 bovine enteric viruses. The bovine hungarovirus was initially identified in both dairy and beef cattle in China. This study elucidates the fecal virome and bacterial community signatures of cattle affected by diarrhea, and reveals novel disease-associated ecological risk factors, including cattle type, cattle age, aquaculture model, and geographical location.IMPORTANCEThe lack of data on the virome and bacterial community restricts our capability to recognize ecological risk factors for bovine diarrhea disease, thereby hindering our overall comprehension of the disease's cause. In this study, we found that, for the diarrheal samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, configuration, and geographic distribution in relation to different disease-associated ecological factors. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. Our study aims to uncover novel ecological risk factors of bovine diarrheal disease by examining the pathogenic microorganism-host-environment disease ecology, thereby providing a new perspective on the control of bovine diarrheal diseases.
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Doenças dos Bovinos , Vírus , Animais , Bovinos , Viroma , Filogenia , Vírus/genética , Bactérias/genética , Diarreia/epidemiologia , Doenças dos Bovinos/epidemiologia , Fatores de RiscoRESUMO
Theranostics technology that combines tumor diagnosis or monitoring with therapy is an important direction for the future development of tumor treatment. It takes advantage of efficiently observing tumor tissues, monitoring tumor treatment in real time, and significantly improving the cure efficiency. Magnetic carbon dots (CDs) are of wide interest as molecular imaging probes, drug carriers, photosensitizers, and radiosensitizers in the integration of tumor fluorescence/magnetic resonance bimodal diagnosis and treatment because of their small size, good optical stability, magnetic relaxation rate, and biocompatibility. This review first analyzes and compares the synthesis methods and physicochemical properties of magnetic CDs in recent years and then concludes their mechanism in tumor fluorescence/magnetic resonance bimodal imaging and therapy in details. Subsequently, the research progress of their application in tumor theranostics are summarized. Finally, the problems and challenges of magnetic CDs for development at this stage are prospected. This review provides new ideas for their controlled synthesis and application in efficient and precise therapy for tumors.
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Neoplasias , Medicina de Precisão , Humanos , Carbono/uso terapêutico , Carbono/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
Vascular endothelial growth factor (VEGF) is an important factor in the development of some diseases such as tumors, ocular neovascular disease and endometriosis. Inhibition of abnormal VEGF expression is one of the most effective means of treating these diseases. The resistance and side effects of currently used VEGF drugs limit their application. Herein, small interfering RNA for VEGF (siVEGF) are developed to inhibit VEGF expression at the genetic level by means of RNA interference. However, as a foreign substance entering the organism, siVEGF is prone to induce an immune response or mismatch, which adversely affects the organism. It is also subjected to enzymatic degradation and cell membrane blockage, which greatly reduces its therapeutic effect. Targeted siVEGF complexes are constructed by nanocarriers to avoid their clearance by the body and precisely target cells, exerting anti-vascular effects for the treatment of relevant diseases. In addition, some multifunctional complexes allow for the combination of siVEGF with other therapeutic tools to improve the treat efficiency of the disease. Therefore, this review describes the construction of the siVEGF complex, its mechanism of action, application in anti-blood therapy, and provides an outlook on its current problems and prospects.
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Neoplasias , Fator A de Crescimento do Endotélio Vascular , Feminino , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Interferência de RNA , RNA Interferente Pequeno , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Disturbance of single-cell transcriptional heterogeneity is an inevitable consequence of persistent donor-specific antibody (DSA) production and allosensitization. However, identifying and efficiently clearing allospecific antibody repertoires to restore single-cell transcriptional profiles remain challenging. Here, inspired by the high affinity of natural bacterial proteins for antibodies, a genetic engineered membrane-coated nanoparticle termed as DSA trapper by the engineering chimeric gene of protein A/G with phosphatidylserine ligands for macrophage phagocytosis was reported. It has been shown that DSA trappers adsorbed alloreactive antibodies with high saturation and activated the heterophagic clearance of antibody complexes, alleviating IgG deposition and complement activation. Remarkably, DSA trappers increased the endothelial protective lineages by 8.39-fold, reversed the highly biased cytotoxicity, and promoted the proliferative profiles of Treg cells, directly providing an obligate immune tolerant niche for single-cell heterogeneity restoration. In the mice of allogeneic transplantation, the DSA trapper spared endothelial from inflammatory degenerative rosette, improved the glomerular filtration rate, and prolonged the survival of allogeneic mice from 23.6 to 78.3 days. In general, by identifying the lineage characteristics of rejection-related antibodies, the chimeric engineered DSA trapper realized immunoadsorption and further phagocytosis of alloantibody complexes to restore the single-cell genetic architecture of the allograft, offering a promising prospect for the treatment of alloantibody-mediated immune injury.
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Transplante de Rim , Camundongos , Animais , Transplante Homólogo , Isoanticorpos , Ativação do Complemento , AloenxertosRESUMO
Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Vírus da Diarreia Epidêmica Suína/fisiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Peptídeo Hidrolases , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/veterinária , Simulação de Acoplamento Molecular , Doenças dos Suínos/tratamento farmacológicoRESUMO
Tissue engineering has a great application prospect as an effective treatment for tissue and organ injury, functional reduction, or loss. Bioactive tissues are reconstructed and damaged organs are repaired by the three elements, including cells, scaffold materials, and growth factors. Graphene-based composites can be used as reinforcing auxiliary materials for tissue scaffold preparation because of their large specific surface area, and good mechanical support. Tissue engineering scaffolds with graphene-based composites have been widely studied. Part of research have focused on the application of graphene-based composites in single tissue engineering. The basic principles of graphene materials used in tissue engineering are summarized in some research. Some studies emphasized the key problems and solutions urgently needed to be solved in the development of tissue engineering and discussed their application prospect. Some related studies mainly focused on the conductivity of graphene and discussed the application of electroactive scaffolds in tissue engineering. In this review, the composite materials for preparing tissue engineering scaffolds are briefly described, which emphasizes the preparation methods, biological properties, and practical applications of graphene-based composite scaffolds. The synthetic techniques, with stressing solvent casting, electrospinning, and three-dimensional printing, are introduced in detail. The mechanical, cell-oriented, and biocompatible properties of graphene-based composite scaffolds in tissue engineering are analyzed and summarized. Their applications in bone tissue engineering, nerve tissue engineering, cardiovascular tissue engineering, and other tissue engineering are summarized systematically. In addition, this work also looks forward to the difficulties and challenges in the future research, providing some references for the follow-up research of graphene-based composites in tissue engineering scaffolds. Impact statement Regeneration and repair of tissue and organ injury has become a new research hotspot in recent years. Tissue engineering scaffolds prepared with graphene-based materials have good biocompatibility, excellent mechanical properties, and strong cell orientation, which can fully induce the proliferation and differentiation of seed cells. This review briefly describes the basic materials for the preparation of tissue engineering scaffolds, and focuses on the preparation, performance, and application of graphene-based materials in tissue engineering, providing sufficient understanding of graphene applied in regenerative medicine.
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Grafite , Alicerces Teciduais , Humanos , Engenharia Tecidual/métodos , Osso e Ossos , Solventes , Materiais Biocompatíveis/farmacologiaRESUMO
Since November 2016, severe infectious diseases characterized by gout and kidney swelling and caused by goose astrovirus (GoAstV) have affected goslings in major goose-producing areas in China. In 2021, a similar serious infectious disease broke out in commercial goose farms in Heilongjiang Province, China. In this study, strain HLJ2021 was successfully isolated from goose embryos. Electron microscopy showed that the viral particles are spherical, with a diameter of about 28 nm. The complete genomic length of strain HLJ2021 is 7210 nt, and it encodes three viral proteins. A phylogenetic analysis showed that strain HLJ2021 belongs to GoAstV-2 (G2). Compared with the two original GoAstV strains, amino acid site 540Q of the strain HLJ2021 spike domain has a mutation that affects the protein structure. One potential recombination event occurred between strains HLJ2021 and AstV/HB01/Goose/0123/19, which led to the generation of recombinant strain AstV/HN03/Goose/0402/19. Strain HLJ2021 also showed strong pathogenicity in goslings. Goslings infected with GoAstV began to die at 48 h post-infection (hpi), with a mortality rate of 83.3% at 240 hpi. At autopsy, visceral urate deposits, severe renal hemorrhage and swelling, and urate in the ureter were observed in the dead goslings. These findings extend our understanding of the evolution of GoAstV, which causes gout. The isolated GoAstV strain HLJ2021 provides a potential resource for the development of biological products for the prevention of goose gout.
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Infecções por Astroviridae , Avastrovirus , Produtos Biológicos , Gota , Doenças das Aves Domésticas , Animais , Infecções por Astroviridae/veterinária , Filogenia , Virulência , Ácido Úrico , Gansos , Avastrovirus/genética , Gota/veterinária , Proteínas Virais/genética , Aminoácidos/genética , China/epidemiologiaRESUMO
Direct contact of membrane molecules and cytokine interactions orchestrate immune homeostasis. However, overcoming the threshold of distance and velocity barriers, and achieving adhesion mediated immune interaction remain difficult. Here, inspired by the natural chemotaxis of regulatory T cells, multifunctionalized FOXP3 genetic engineered extracellular vesicles, termed Foe-TEVs, are designed, which display with adhesive molecules, regulatory cytokines, and coinhibitory contact molecules involving CTLA-4 and PD-1, by limited exogenous gene transduction. Foe-TEVs effectively adhere to the tubular, endothelial, and glomerular regions of allogeneic injury in the renal allograft, mitigating cell death in situ and chronic fibrosis transition. Remarkably, transcript engineering reverses the tracking velocity of vesicles to a retained phenotype and enhanced arrest coefficient by a factor of 2.16, directly interacting and attenuating excessive allosensitization kinetics in adaptive lymphoid organs. In murine allogeneic transplantation, immune adhesive Foe-TEVs alleviate pathological responses, restore renal function with well ordered ultrastructure and improved glomerular filtration rate, and prolong the survival period of the recipient from 30.16 to 92.81 days, demonstrating that the delivery of extracellular vesicles, genetically engineered for immune adhesive, is a promising strategy for the treatment of graft rejection.
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Vesículas Extracelulares , Transplante de Rim , Camundongos , Animais , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/genética , Transplante Homólogo , Linfócitos T Reguladores/metabolismoRESUMO
Purpose: Parvovirus B19 (B19V) infection is a viral threat after kidney transplantation. It is mainly transmitted by close-contact inhalation of aerosolized viral particles. The risk of nosocomial spread of B19V in the transplantation ward is quite high. This study aimed to evaluate the quality of routine disinfection and the effectiveness of isolation measures in the wards of B19V-infected kidney transplant recipients. Patients and Methods: Throat swab samples of 19 kidney transplant recipients admitted to the isolation ward and three healthcare workers (HCWs) were collected for viral DNA detection. Routine disinfection procedures were performed twice a day in general and B19V isolation wards. Environmental surface and air samples were collected for viral DNA detection before and after disinfection. Results: A total of four patients were diagnosed with B19V infection and transferred to the B19V isolation ward, of which only two had positive throat swab samples. The other 15 patients and all HCWs tested negative for B19V. A total of 88 environmental surface and air samples were collected. Eight of the environmental samples collected in the B19V isolation ward before disinfection tested positive for B19V, while one sample tested positive after disinfection. In the general wards, all environmental samples collected before disinfection tested negative for B19V. All 24 samples collected from ambient air, whether in B19V isolation or general wards, before or after disinfection, tested negative for B19V. Conclusion: Existing methods of routine or terminal disinfection for air and object surfaces were effective in eliminating B19V from object surfaces and ambient air in the isolation and general wards. Material surfaces that are exposed to high frequency and easily contaminated by blood, body fluids, and indoor air were the focus of cleaning and disinfection. Nosocomial cross-infection of other immunocompromised patients and HCWs can be avoided if appropriate prevention and control measures are taken.
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With increasing knowledge about diseases at the histological, cytological to sub-organelle level, targeting organelle therapy has gradually been envisioned as an approach to overcome the shortcomings of poor specificity and multiple toxic side effects on tissues and cell-level treatments using the currently available therapy. Organelle carbon dots (CDs) are a class of functionalized CDs that can target organelles. CDs can be prepared by a "synchronous in situ synthesis method" and "asynchronous modification method." The superior optical properties and good biocompatibility of CDs can be preserved, and they can be used as targeting particles to carry drugs into cells while reducing leakage during transport. Given the excellent organelle fluorescence imaging properties, targeting organelle CDs can be used to monitor the physiological metabolism of organelles and progression of human diseases, which will provide advanced understanding and accurate diagnosis and targeted treatment of cancers. This study reviews the methods used for preparation of targeting organelle CDs, mechanisms of accurate diagnosis and targeted treatment of cancer, as well as their application in the area of cancer diagnosis and treatment research. Finally, the current difficulties and prospects for targeting organelle CDs are prospected.
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Neoplasias , Pontos Quânticos , Carbono , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Imagem Óptica , OrganelasRESUMO
Carbon dots (CDs) have shown great potential in drug delivery and biological imaging applications. In this work, a doxorubicin (DOX) delivery carrier and imaging probe for liver cancer-targeted therapy was designed based on CDs with high fluorescence quantum yield (97%), aiming to enhance the antitumor activity and imaging efficiency. Folic acid (FA), which showed high expression in hepatoma cells, was used as targeting components to modify CDs (FA-CDs), and then FA-CDs-DOX was obtained by loading DOX. Results show that CDs and FA-CDs have good biocompatibility, and the DOX release from FA-CDs-DOX is targeted and selective. Confocal microscope demonstrates that FA-CDs-DOX has excellent ability of fluorescence imaging in liver cancer cells. The imaging in vivo shows the fluorescence intensity of FA-CDs-DOX is strong enough to penetrate tumor tissue and skin, further verifying its enhanced-fluorescent imaging effects. Tumor inhibition in vivo indicates that the targeting ability of FA-CDs-DOX is significantly higher than that of free DOX, showing obvious better therapeutic effect. To sum up, the targeted and fluorescent drug delivery system based on CDs with high fluorescence quantum yield show an excellent imaging in vivo and tumor inhibition effect, which provide a novel strategy for promoting the potential clinical application of CDs in liver cancer treatment.
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Carbono , Neoplasias Hepáticas , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Ácido Fólico , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Folic acid-conjugated magnetic ordered mesoporous carbon nanospheres (FA-MOMCNs) are developed as a targeting delivery vehicle of doxorubicin (DOX) in this work. Investigations on DOX loading mechanism show that the loading capacity of FA-MOMCNs is up to 577.12â¯mgâ¯g-1 by means of both physical porous adsorption and covalent interactions, and the pH-dependent drug release is achieved. Excellent biocompatibility of FA-MOMCNs with blood and cells is confirmed by hemolysis and cytotoxicity assays. With the assistance of effective passive and active targeting, DOX-loading FA-MOMCNs can be readily internalized into cancer cell, where the carried DOX can be efficiently released in the acidic microenvironment of the cancer cell for its proliferation inhibition. This controlled release and targeting vehicle of DOX makes it possible to reduce the toxic effect to normal tissues during circulation in the body and is promising for highly efficient chemotherapy.
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Carbono/química , Doxorrubicina/química , Ácido Fólico/química , Nanosferas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Células HeLa , Humanos , Células MCF-7 , Fenômenos Magnéticos , Magnetismo/métodos , PorosidadeRESUMO
Chiral carbon quantum dots (CQDs) with chirality, fluorescence and biocompatibility were synthesized by a one-step method with l-/d-tryptophan (l-/d-Trp), as both carbon source and chiral source. Levogyration-/dextrorotation-CQDs (l-/d-CQDs) were characterized by transmission electron microscopy, Fourier transform infrared spectrometry, ultraviolet-visible absorption, excitation and emission spectrometry and circular dichroism (CD) spectrometry. Results show that l-CQDs and d-CQDs present similar spherical morphology, functional groups and optical properties. The CD signal, around 220, 240 and 290 nm are opposite and symmetric, which conclusively demonstrates that l-CQDs and d-CQDs are enantiomers. Besides the CD signal around 220 nm from the inheritance of l-/d-Trp, two new chiral signals around 240 and 290 nm were induced by chiral environment.
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To improve the bio-solubility and sustained-release properties of a carbon nanotube (CNT)-drug complex, the present study used a hydrophilic polymer, polyethylene glycol (PEG), and ß-estradiol (E2), which targets the estrogen receptor in human breast cancer cells (HBCCs), to modify CNTs carrying lobaplatin (LBP) to form E2-PEG-CNT-LBP. The in vitro inhibitory effects against HBCCs and the in vivo pharmacological effect of the complex on heart, liver and kidney tissues were also evaluated. The results indicated that the inhibitory effects of this complex against HBCCs reached 80.44% within 72 h. A blood biochemical test of normal mice indicated that this complex reduced platelet counts, while aspartate aminotransferase levels were increased compared with those in the control group. Histopathological analysis revealed no obvious adverse effects on the heart, liver and kidneys. The in vivo results indicated that the novel E2-PEG-CNT-LBP complex had no obvious toxic effects while exhibiting sustained-release properties. The clearance of E2-PEG-CNT-LBP by non-specific uptake systems was delayed and its clearance was increased compared with LBP alone.
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A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy.
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Carbono/química , Portadores de Fármacos/química , Hipertermia Induzida/métodos , Magnetismo , Nanosferas/química , Doxorrubicina/química , Doxorrubicina/metabolismo , Liberação Controlada de Fármacos , Óxido Ferroso-Férrico/química , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Temperatura , Termogravimetria , Difração de Raios XRESUMO
Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.