RESUMEN
Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.
Asunto(s)
Nanotecnología , Investigación Biomédica Traslacional , Materiales Biocompatibles , Nanoestructuras/toxicidadRESUMEN
To increase the anti-tumor activity of paclitaxel (PTX), novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) were developed. In vitro, characteristics of PTX-TSL were evaluated. The mean particle diameter was about 100 nm, and the entrapment efficiency was larger than 95%. The phase-transition temperature of PTX-TSL determined by differential scanning calorimetry was about 42 °C. The result of in vitro drug release from PTX-TSL illustrated that release rate at 37 °C was obviously lower than that at 42 °C. Stability data indicated that the liposome was physically and chemically stable for at least 3 months at -20 °C. In vivo study, after three injections with hyperthermia in the xenograft lung tumor model, PTX-TSL showed distinguished tumor growth suppression, compared with non-temperature-sensitive liposome and free drug. The results of intratumoral drug concentration indicated that PTX-TSL combined with hyperthermia delivered more paxlitaxel into the tumor location than the other two paxlitaxel formulations. In summary, PTX-TSL combined with hyperthermia significantly inhibited tumor growth, due to the increased targeting efficiency of PTX to tumor tissues. Such approach may enhance the delivery efficiency of chemotherapeutics into solid tumors.
Asunto(s)
Doxorrubicina/farmacocinética , Neoplasias Pulmonares/fisiopatología , Paclitaxel/farmacocinética , Línea Celular Tumoral , Química Farmacéutica , Doxorrubicina/química , Liberación de Fármacos , Fiebre , Humanos , Liposomas , Neoplasias Pulmonares/química , Paclitaxel/química , Temperatura de Transición , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To construct the interleukin-18-PE38 fusion gene expression vector and explore the expression of the fusion gene in the chondrocyte. METHODS: The recombinant eukaryotic expression vector PsecTag2B-IL-18-PE38 was constructed by inserting interleukin-18-PE38 fusion gene into eukaryotic expression vector PsecTag2B with molecular cloning technique. It was confirmed by restrictive enzymes (EcoR I) digestion assay and PCR. The vector was transfected into primary chrondrocyte by liposome protocol, and the transient expression was identified by fluorescence immunocytochemical assay. RESULTS: Restrictive enzymes digestion analysis and PCR revealed that the interleukin-18-PE38 fusion gene was cloned into the eukaryotic expression vector PsecTag2B successfully. Immunofluorescence photograph of fluorescence immunocytochemical method confirmed that the fusion gene can be expressed in the cytomembrane and cytoplasm. CONCLUSION: The results confirmed that PsecTag2B-IL-18-PE38 fusion gene can be expressed in the chondrocyte, which could serve as a foundation for the study on rheumatoid arthritis therapy.
Asunto(s)
ADP Ribosa Transferasas/genética , Toxinas Bacterianas/genética , Condrocitos/metabolismo , Exotoxinas/genética , Interleucina-18/genética , Proteínas Recombinantes de Fusión/biosíntesis , Factores de Virulencia/genética , ADP Ribosa Transferasas/biosíntesis , Animales , Animales Recién Nacidos , Toxinas Bacterianas/biosíntesis , Células Cultivadas , Condrocitos/citología , Células Eucariotas/metabolismo , Exotoxinas/biosíntesis , Vectores Genéticos , Factores Inmunológicos/metabolismo , Interleucina-18/biosíntesis , Liposomas , Ratones , Proteínas Recombinantes de Fusión/genética , Transfección , Factores de Virulencia/biosíntesis , Exotoxina A de Pseudomonas aeruginosaRESUMEN
AIM: To construct a novel eukaryotic expression plasmid including the recombinant immunotoxin DT390-mRantes and treat experimental autoimmune encephalomyelitis (EAE) in mice. METHODS: EAE in C57BL/6 mice were induced by the extracted MBP. The mRantes fragment was inserted into the eukaryotic expression plasmid SRalpha containing DT390. Then cationic liposome-embedded plasmid DNA was injected into the muscles of the hind-limbs in mice. The effect of DT390-mRantes was evaluated by observing clinical symptoms, pathological changes of brain, relative cytokine of peripheral blood, and the proportion of T cells and B cells. RESULTS: The recombinant immunotoxin DT390-mRantes was successfully constructed. Compared the mice in treated group with those in untreated group the clinical symptoms of EAE were alleviated, the infiltration of inflammatory cells were decreased, the IFN-gamma level was fallen, and the ratio of T/B cells was decreased. CONCLUSION: The recombinant immunotoxin DT390-mRantes has distinct effects on EAE in mice, which may be used for beneficial reference to the therapy of MS.