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Objective:To prepare liquid-gas phase modified nanoparticles (TMZ/PFP/PLGA NPs) of perfluoropentane (PFP) and temozolomide (TMZ) encapsulated by polylactic-glycolic acid copolymer (PLGA), combined with low intensity focused ultrasound (LIFU) irradiation, and to investigate its ultrasound imaging ability and intervention effect on human glioma cells in vitro.Methods:TMZ/PFP/PLGA NPs were prepared by compound emulsion method. The basic physical and chemical properties and drug loading ability of TMZ/PFP/PLGA NPs were detected. CCK-8 assay was used to detect the cytotoxicity of nanoparticles in vitro and the effect of synergistic intervention with LIFU on the survival rate of glioma cells. The expression levels of apoptosis related proteins Bcl-2, Bax and caspase-3 were detected by Western blot.Results:Under transmission electron microscope, TMZ/PFP/PLGA NPs showed a circular core-shell structure with regular morphology, particle size was (137.9±63.31)nm, encapsulation efficiency of TMZ was (83.01±5.57)%, drug loading was (3.19±0.22)%. The survival rate of U251 cells was still above 70% after 24 hours of co-incubation with nanoparticles. Under the synergistic effect of LIFU irradiation, the apoptosis of U251 cells was accelerated and the survival rate of U251 cells was significantly decreased. The results of Western blot showed that the synergic intervention could significantly down-regulate the expression of apoptosis related protein Bcl-2, and significantly up-regulate the expression of Bax protein and caspase-3 protein (all P<0.05). Conclusions:TMZ/PFP/PLGA NPs have good basic physical and chemical properties. TMZ/PFP/PLGA NPs have low cytotoxicity in vitro while efficiently loading chemotherapeutic drug timozolomide. Synergistic intervention under LIFU irradiation can significantly accelerate the apoptosis of U251 glioma cells, which has a good application prospect.
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Small interfering RNA (siRNA) has been used to treat various skin diseases. However, siRNA is limited in application due to its electronegativity, strong polarity, easy degradation by nuclease and difficulty in breaking through the skin barrier. Therefore, safe and efficient siRNA delivery vector is the premise of effective treatment of skin diseases by siRNA. In recent years, with the deepening of research on siRNA, great progress has been made in the development of delivery systems based on lipids, polymers, peptides and nanoparticles, some new transdermal delivery vectors of siRNA have emerged, such as liposomes, dendrimers, cell penetrating peptides, and spherical nucleic acid nanoparticles. This review will focus on the recent advance in siRNA transdermal delivery vectors.
Subject(s)
Humans , Administration, Cutaneous , Genetic Vectors , RNA, Small Interfering , Skin Diseases , TherapeuticsABSTRACT
Polyamidoamine (PAMAM) dendrimers as synthetic gene vectors are efficient gene delivery systems. In this study, a kind of α-cyclodextrin-PAMAM conjugates polymer (CyD-G1) was synthesized as a gene delivery vector. Based on 1H NMR detectation, about 6.4 PAMAM-G1 molecules was grafted onto an α-CD core. Agarose gel electrophoresis revealed that CyD-G1 could efficiently bind with DNA to condense them into nano-scale particles, which showed a similar binding capacity of PEI-25K. Besides, it could protect DNA from DNase I degradation in a low N/P ratio. When N/P ratio in the CyD-G1/DNA polyplex was 40, the average particle size of CyD-G1/DNA polyplex was about 120 nm, and zeta potential was +21 mV. This polyplex could maintain its particle size in serum-containing solution within 360 min. In comparison with PEI-25K carrier, CyD-G1 showed low cytotoxicity in various cell lines. Cell transfection results showed that CyD-G1 efficiently delivered DNA into cells at N/P=80 compared with Lipofectamine 2000 and PEI-25K.Unlike Lipofectamine 2000 and PEI-25K, in serum-containing test condition, CyD-G1/DNA polyplex could maintain the transgene activities. The results of confocal laser scanning microscopy indicated that most DNA entered into cell nuclei within 4 h, and this phenomenon was consistent with the results calculated by flow cytometry. Taken together, CyD-G1 showed good transgene activities and the gene delivery vector could be used not only in vitro but also in vivo.
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Currently, polyethylenimine(PEI) is one of the most promising non-viral gene delivery vectors. However, high relative molecular mass PEI has obvious toxicity and is short of targeting or specificity to cells or tissues. As we know targeting or specificity is the key property of ideal gene delivery systems. Therefore, PEI should be modified to become a gene vector with targeting and low toxicity. Up to now investgations on modification of PEI for targeting effect mainly include:1.modification with endogenous ligands such as transferrin Tf RGD peptide etc 2.modification with carbohydrate such as galactose etc 3.modification with specific antibody. Of these, the specific antibody-directed PEI is anticipated to be one of promising and distinctive targeting gene delivery carriers. The present paper summarises literature on PEI as targeted gene delivery vectors.
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Currently, polyethylenimine(PEI) is one of the most promising non-viral gene delivery vectors. However, high relative molecular mass PEI has obvious toxicity and is short of targeting or specificity to cells or tissues. As we know, targeting or specificity is the key property of ideal gene delivery systems. Therefore, PEI should be modified to become a gene vector with targeting and low toxicity. Up to now, investgations on modification of PEI for targeting effect mainly include:1.modification with endogenous ligands such as transferrin(Tf),RGD peptide, etc;2.modification with carbohydrate such as galactose,etc;3.modification with specific antibody. Of these, the specific antibody-directed PEI is anticipated to be one of promising and distinctive targeting gene delivery carriers. The present paper summarises literature on PEI as targeted gene delivery vectors.
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OBJECTIVE: Mucosal surfaces are a major portal of entry for many human pathogens that are the cause of infectious diseases. Vaccines that immunize by mucosal routes may induce protective immunity against mucosal pathogens at their sites of entry thus to be more effective and economical. We try to overview the status and progress of research on mucosal vaccines. METHODS: The databases of CNKI and Pubmed were used to search the related articles about mucosal vaccines with key words "mucosal vaccine, mucosal adjuvant, mucosal particulate delivery vectors" in Chinese and English. Articles closely related to mucosal vaccines were selected. RESULTS: Thirty-six articles were included at last. Live-attenuated or inactivated mucosal vaccines and vaccines based on new concepts such as subunit vaccines, virus-like particles and virosomes have been marketed, and related research work are undergoing. Safe and effective mucosal adjuvants and delivery vectors are being sought to enhance the magnitude and quality of the protective immune response. The composition, size, surface chemistry and ligands of particulate carrier systems may influence the efficacy. Great progress has been made in several particulate delivery systems. CONCLUSION: Although the research and development of mucosal vaccines are facing many difficulties and challenges, the progress of research work will bring new opportunities to mucosal vaccines development.
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Objective To modify polyargine (PLR) with polyethylene glycol (PEG) and to observe the effect of PEG modilication on PLR cytotoxicity and efticiency of PLR-mediated RNA interference. Methods1 HNMR was used to characterize PLR-PEG and gel electrophoresis was adopted to determine the siRNA-packing capacity of PLR-PEG. The cytotoxicity of PLR-PEG, cellular uptake and RNA interference efficiency of PLR-PEG/siRNA complexes were investigated using prostate cancer stem-like cells(RC-92a/hTERT). Results1 HNMR results showed the successful synthesis of PLR-PEG. It was found that PEG modiiication decreased cytotoxicity of PLR and reduced cellular uptake of PLR/siRNA complexes, but the reduction of cellular uptake was limited when N/P was high. The modiiication also inhibited the efticiency of PLR-mediated RNA interference, but the influence of PEG moditication was not notable within a certain range. Conclusion PEG-moditied PLR may be a promising vector for gene therapy targeting prostate cancer stem cells.
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An adult cell originates from stem cell. The stem cell is usually categorized into three species including an embryonic stem cell (ESc), an adult stem cell, and an induced stem cell (iPSc). iPSc features pluripotency, which is meant to be differentiated into any types of cells. Accordingly, it is much attractive to anyone who pursuit a regenerative medicine, owing to the potential almighty. They are simply produced by reprogramming a somatic cell via a transfer of transcription factors. The efficiency and productivity of iPS are considerably subject to delivering methods of exogenous genes into a variety of targeted mammalians. Conventional and well-run gene delivery techniques have been reviewed here. This details the methods and principles of delivery factors and provides an overview of the research, with an emphasis on their potential for use as clinical therapeutic platforms.