This study was carried out to investigate the transfection effect of exogenous gene into plant protoplast cell mediated by polyethylenimine （PEI） nanovector, based on PEI gene delivery system in the field of medical...This study was carried out to investigate the transfection effect of exogenous gene into plant protoplast cell mediated by polyethylenimine （PEI） nanovector, based on PEI gene delivery system in the field of medical science. PEI/DNA complexes were prepared by using PEI polymer to bind the plant expression plasmid, pCMl205-GFPn. The ability of PEI combining and protecting DNA was investigated by agarose gel electrophoresis retardation assay. The surface characteristics of PEI/DNA complexes were observed with transmission electron microscope. The transfection efficiency of Arabidopsis thaliana protoplasts mediated by PEI/DNA complexes at different N/P ratios was analyzed based on observation of transient expression of green fluorescent protein with confocal laser scanning microscope. PEI could bind and condense DNA, and form stable 100-200 nm PEI/DNA complexes when the proportion of PEl and DNA is in the range of 5：1-1：4. Transfection efficiency of PEI/DNA complexes increased with N/P ratios in range of N/P〈5 and reached the highest at N/P=5, and began to decrease beyond N/P〉5 as higher toxicity to cells. The transfection efficiency of PEI/DNA complexes at N/P=5 was higher than PEG. This study confirmed that PEI nanovector could effectively mediate foreign gene entering into A. thaliana protoplast cell to obtain transient expression, which may be developed as a hopeful and novel transgenic method combined with plant protoplast regeneration.展开更多
Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between ...Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovectorbased anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.展开更多
Small interfering RNA （siRNA） therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery b...Small interfering RNA （siRNA） therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with cova- lent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired struc^rally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self- assembling amphiphilic dendrimers to construct supramo- lecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great pro- mise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.展开更多
The respiratory system, as well as the skin, are organs in direct contact with the environment and it they represent possible doors for the entrance of therapeutic agents into the body. Because of the increasing incid...The respiratory system, as well as the skin, are organs in direct contact with the environment and it they represent possible doors for the entrance of therapeutic agents into the body. Because of the increasing incidence of pulmonary diseases with high mortality and morbidity, pulmonary drug delivery is emerging as a non-invasive and attractive approach for the treatment of several pathologies. It must be pointed out that the development of drug delivery systems for pulmonary application requires a detailed knowledge of the lung, both in its healthy and disease state. Among the various drug delivery systems considered for pulmonary application, nanocarriers show several advantages over other conventional approaches for the treatment of respiratory diseases, for example prolonged drug release and cell-specific targeted drug delivery. Nano-size drug carriers can incorporate various therapeutics (e.g., poorly water soluble drugs, macromolecules) and show interesting features as drug delivery systems to the lung, such as: controlled release, protection from metabolism and degradation, decreased drug toxicity and targeting capabilities. Since gene therapy (e.g. small interfering RNA, siRNA) is currently being developed for a wide range of acute and chronic lung diseases, including CF, cancer and asthma, the use of nanocarriers for lung release/targeting represents a promising application of such nano-sized structures. Despite the many promising proof of concepts of various delivery technologies reported in this review, further efforts are needed to ensure the safety of long-term in vivo applications and the development of scale up from laboratory to industry in order to reach, together with safety, large - scale production at affordable costs of innovative lung delivery technologies.展开更多
We demonstrate that it is possible to form non-phospholipid fluid bilayers in aqueous milieu with a mixture of palmitic acid (PA),cholesterol (Chol),and cholesterol sulfate (Schol) in a molar proportion of 30/28/42.Th...We demonstrate that it is possible to form non-phospholipid fluid bilayers in aqueous milieu with a mixture of palmitic acid (PA),cholesterol (Chol),and cholesterol sulfate (Schol) in a molar proportion of 30/28/42.These self-assemblies are shown to be bilayers in the liquid ordered phase.They are stable between pH 5 and 9.Over this pH range,the protonation/deprotonation of PA carboxylic group is observed but this change does not appear to alter the stability of these bilayers,a behavior contrasting with that observed for binary mixtures of PA/Chol,and PA/Schol.The multilamellar dispersions formed spontaneously from the PA/Chol/Schol mixture could be successfully extruded to form Large Unilamellar Vesicles (LUVs).These LUVs show interesting permeability properties,linked with their high sterol content.These non-phospholipid liposomes can sustain a pH gradient (pH internal 8/pH external 6) 100 times longer than LUVs made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol,with a molar ratio of 60/40.Moreover,the non-phospholipid LUVs are shown to protect ascorbic acid from an oxidizing environment (1 mM iron(III)).Once entrapped in liposomes,ascorbic acid displays a degradation rate similar to that obtained in the absence of iron(III).These results show the possibility to form novel nanocontainers from a mixture of a monoalkylated amphiphile and sterols,with a good pH stability and showing interesting permeability properties.展开更多
基金supported by the National High Technology R&D Program of China (2006AA10A203)the Genetically Modified Organisms Breeding Major Projects, Ministry of Agriculture, China (2009ZX09010-006B)
文摘This study was carried out to investigate the transfection effect of exogenous gene into plant protoplast cell mediated by polyethylenimine （PEI） nanovector, based on PEI gene delivery system in the field of medical science. PEI/DNA complexes were prepared by using PEI polymer to bind the plant expression plasmid, pCMl205-GFPn. The ability of PEI combining and protecting DNA was investigated by agarose gel electrophoresis retardation assay. The surface characteristics of PEI/DNA complexes were observed with transmission electron microscope. The transfection efficiency of Arabidopsis thaliana protoplasts mediated by PEI/DNA complexes at different N/P ratios was analyzed based on observation of transient expression of green fluorescent protein with confocal laser scanning microscope. PEI could bind and condense DNA, and form stable 100-200 nm PEI/DNA complexes when the proportion of PEl and DNA is in the range of 5：1-1：4. Transfection efficiency of PEI/DNA complexes increased with N/P ratios in range of N/P〈5 and reached the highest at N/P=5, and began to decrease beyond N/P〉5 as higher toxicity to cells. The transfection efficiency of PEI/DNA complexes at N/P=5 was higher than PEG. This study confirmed that PEI nanovector could effectively mediate foreign gene entering into A. thaliana protoplast cell to obtain transient expression, which may be developed as a hopeful and novel transgenic method combined with plant protoplast regeneration.
文摘Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovectorbased anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.
文摘Small interfering RNA （siRNA） therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with cova- lent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired struc^rally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self- assembling amphiphilic dendrimers to construct supramo- lecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great pro- mise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.
文摘The respiratory system, as well as the skin, are organs in direct contact with the environment and it they represent possible doors for the entrance of therapeutic agents into the body. Because of the increasing incidence of pulmonary diseases with high mortality and morbidity, pulmonary drug delivery is emerging as a non-invasive and attractive approach for the treatment of several pathologies. It must be pointed out that the development of drug delivery systems for pulmonary application requires a detailed knowledge of the lung, both in its healthy and disease state. Among the various drug delivery systems considered for pulmonary application, nanocarriers show several advantages over other conventional approaches for the treatment of respiratory diseases, for example prolonged drug release and cell-specific targeted drug delivery. Nano-size drug carriers can incorporate various therapeutics (e.g., poorly water soluble drugs, macromolecules) and show interesting features as drug delivery systems to the lung, such as: controlled release, protection from metabolism and degradation, decreased drug toxicity and targeting capabilities. Since gene therapy (e.g. small interfering RNA, siRNA) is currently being developed for a wide range of acute and chronic lung diseases, including CF, cancer and asthma, the use of nanocarriers for lung release/targeting represents a promising application of such nano-sized structures. Despite the many promising proof of concepts of various delivery technologies reported in this review, further efforts are needed to ensure the safety of long-term in vivo applications and the development of scale up from laboratory to industry in order to reach, together with safety, large - scale production at affordable costs of innovative lung delivery technologies.
基金financially supported by the Natural Sciences and Engineering Research Council of Canadaby the Fonds Québécois de la Recherche sur la Nature et les Technologies through its Strategic Clusterprogram
文摘We demonstrate that it is possible to form non-phospholipid fluid bilayers in aqueous milieu with a mixture of palmitic acid (PA),cholesterol (Chol),and cholesterol sulfate (Schol) in a molar proportion of 30/28/42.These self-assemblies are shown to be bilayers in the liquid ordered phase.They are stable between pH 5 and 9.Over this pH range,the protonation/deprotonation of PA carboxylic group is observed but this change does not appear to alter the stability of these bilayers,a behavior contrasting with that observed for binary mixtures of PA/Chol,and PA/Schol.The multilamellar dispersions formed spontaneously from the PA/Chol/Schol mixture could be successfully extruded to form Large Unilamellar Vesicles (LUVs).These LUVs show interesting permeability properties,linked with their high sterol content.These non-phospholipid liposomes can sustain a pH gradient (pH internal 8/pH external 6) 100 times longer than LUVs made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol,with a molar ratio of 60/40.Moreover,the non-phospholipid LUVs are shown to protect ascorbic acid from an oxidizing environment (1 mM iron(III)).Once entrapped in liposomes,ascorbic acid displays a degradation rate similar to that obtained in the absence of iron(III).These results show the possibility to form novel nanocontainers from a mixture of a monoalkylated amphiphile and sterols,with a good pH stability and showing interesting permeability properties.
