RESUMEN
Removal of pharmaceutical ingredients such as tetracycline from aqueous solution has a great importance. The aim of the current study was to investigate the degradation of tetracycline antibiotic in the presence of a triode semiconductor oxide as well as modeling of the photocatalytic degradation process in order to determine optimal condition Zinc stannate nanoflower (Zn2SnO4) was synthesized by hydrothermal process and characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) techniques. Response surface methodology (RSM) was used to model and optimize four key independent variables, including photocatalyst dosage, initial concentration of tetracycline antibiotic (TC) as model pollutant, pH and reaction time of photocatalytic degradation. The proposed quadratic model was in accordance with the experimental results with a correlation coefficient of 98%. The obtained optimal experimental conditions for the photodegradation process were the following: zinc stannate (ZTO) dosage=300â¯mgâ¯L-1, initial concentration of TC= 10â¯mgâ¯L-1, reaction time= 100â¯min and pH=4.5. Under the optimal conditions, the predicted degradation efficiency was 95.45% determined by the proposed model. In order to evaluate the accuracy of the optimization procedure, the confirmatory experiment was carried out under the optimal conditions and the degradation efficiency of 93.54% was observed, which closely agreed with the predicted value.
Asunto(s)
Antineoplásicos/administración & dosificación , Quimiotaxis , Liposomas/administración & dosificación , Magnetosomas , Neoplasias/tratamiento farmacológico , Oxígeno/metabolismo , Hipoxia Tumoral/fisiología , Aerobiosis/fisiología , Animales , Quimiotaxis/fisiología , Portadores de Fármacos/química , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Cocos Anaerobios Gramnegativos/metabolismo , Células HCT116 , Humanos , Liposomas/farmacocinética , Magnetosomas/química , Magnetosomas/metabolismo , Ratones , Nanopartículas/administración & dosificación , Neoplasias/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.
Asunto(s)
Alphaproteobacteria , Neoplasias Colorrectales/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Compuestos Férricos , Campos Magnéticos , Nanopartículas/química , Neoplasias Experimentales/tratamiento farmacológico , Animales , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Compuestos Férricos/química , Compuestos Férricos/farmacología , Células HCT116 , Humanos , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Hipoxia/patología , Ratones , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Ratas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications.
Asunto(s)
Neoplasias de la Mama/patología , Proliferación Celular/genética , Sistemas de Liberación de Medicamentos , Grafito/química , Nanopartículas/administración & dosificación , Óxidos/química , ARN Interferente Pequeño/genética , Neoplasias de la Mama/genética , Péptidos de Penetración Celular , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Femenino , Silenciador del Gen , Humanos , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , Células Tumorales CultivadasRESUMEN
The targeted and effective delivery of therapeutic agents remains an unmet goal in the field of controlled release systems. Magnetococcus marinus MC-1 magnetotactic bacteria (MTB) are investigated as potential therapeutic carriers. By combining directional magnetotaxis-microaerophilic control of these self-propelled agents, a larger amount of therapeutics can be delivered surpassing the diffusion limits of large drug molecules toward hard-to-treat hypoxic regions in solid tumors. The potential benefits of these carriers emphasize the need to develop an adequate method to attach therapeutic cargos, such as drug-loaded nanoliposomes, without substantially affecting the cell's ability to act as delivery agents. In this study, we report on a strategy for the attachment of liposomes to MTB (MTB-LP) through carbodiimide chemistry. The attachment efficacy, motility, and magnetic response of the MTB-LP were investigated. Results confirm that a substantial number of nanoliposomes (â¼70) are efficiently linked with MTB without compromising functionality and motility. Cytotoxicity assays using three different cell types (J774, NIH/3T3, and Colo205) reveal that liposomal attachments to MTB formulation improve the biocompatibility of MTB, whereas attachment does not interfere with liposomal uptake.
Asunto(s)
Bacterias/metabolismo , Portadores de Fármacos , Liposomas/química , Nanopartículas/química , Nanotecnología/métodos , Alphaproteobacteria/metabolismo , Animales , Antineoplásicos/química , Materiales Biocompatibles/química , Carbodiimidas/química , Línea Celular Tumoral , Separación Celular , Difusión , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Vectores Genéticos , Humanos , Concentración 50 Inhibidora , Magnetismo , Ratones , Microscopía Confocal , Células 3T3 NIH , Neoplasias/tratamiento farmacológico , Unión ProteicaRESUMEN
We showed that magnetotactic bacteria (MTB) have great potentials to be used as microcarriers for targeted delivery of therapeutic agents. Indeed, magnetotaxis inherent in MTB can be exploited to direct them towards a tumor while being propelled by their own flagellated molecular motors. Nonetheless, although the thrust propelling force above 4 pN of the MC-1 MTB showed to be superior compared to other technologies for displacement in the microvasculature, MTB becomes much less efficient when travelling in larger blood vessels due to higher blood flow. In the latter case, a new technique developed by our group and referred to as Magnetic Resonance Navigation (MRN), has been successfully applied in larger vessels using synthetic microcarriers nut proved to be less efficient in the microvasculature due mainly to technological constraints. These findings called for the need to integrate both approaches by encapsulating MTB in special MRN-compatible microcarriers to be release in the vicinity of microvascular networks where they becomes more effective for targeting purposes in tumoral lesions. In this study Magnetococcus strain MC-1 were encapsulated in giant vesicles. The survival of the encapsulated bacteria was monitored. The release of bacteria from giant vesicles was also studied in different time intervals and conditions.