Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses

Hedley, Mary Lynne; Curley, Joanne; Urban, Robert G.

doi:10.1038/nm0398-365

Cited by 222 publications

(107 citation statements)

References 10 publications

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“…38,69 The encapsulation of pDNA within microspheres or NPs has also been shown to preserve their in vivo functional integrity when the contact time with lysosomal enzymes is shortened. 37,70,71 Prior research that followed the kinetics of tissue and cellular localization of NPs loaded with either Rh-6G or Nile red also showed that the injected NPs reach the retina rapidly, homing in on the RPE cells where they were still observed 4 months after the injection; encapsulated Rh-6G dye diffused slowly from the NPs and uniformly stained the retinal layers. 72 RPE cells, as main constituents in CNV, are known to quickly respond and adapt to environmental stresses such as ischemia and metabolic changes by expressing a number of various genes, 73 and have a major role in CNV because of their essential function in neural retina homeostasis.…”

Section: Pdna-loaded Nanoparticles Inhibit Cnv C Zhang Et Almentioning

confidence: 99%

“…Besides, antigens or DNA fragments encapsulated in PLGA matrix can be protected from endonuclease activity. 37,38 Biodegradation and ocular tissue reaction to microspheres or NPs of poly (D, L-lactide) or PLGA have been studied earlier in vitro 39,40 and in vivo. [41][42][43][44] In this study, we showed the inhibitory efficiency of shRNA-expressing plasmid DNA (pDNA) targeting HIF1a (pshHIF-1a) on laser-induced CNV in rats, and further evaluated the therapeutic potential of PLGA NPs as a non-viral vector for pshHIF-1a gene transfection to the posterior segment of eyes.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1a (HIF-1a) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1a NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1a NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1a NPs group (Po0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF1a NPs-treated group was significantly smaller than other groups (Po0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1a NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

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Section: Pdna-loaded Nanoparticles Inhibit Cnv C Zhang Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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“…28 We have developed novel biodegradable PLG microparticles stabilized by the cationic surfactant, CTAB which have been shown to be a highly effective adjuvant formulation for DNA vaccination. The microparticles were prepared with a mean size of 1 m, and exhibited a net positive surface charge (Z = 40 mV) allowing for adsorption of plasmid DNA.…”

Section: Sf2 Formulated On Plg-ctab Microparticles Following a 24 H mentioning

confidence: 99%

Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells

et al. 2000

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Dendritic cells (DC) play a key role in antigen presentation and activation of specific immunity. Much current research focuses on harnessing the potency of DC for vaccines, gene therapy, and cancer immunotherapy applications. However, DC are not readily transfected in vitro by traditional nonviral techniques. A novel DNA vaccine formulation was used to determine if DC are transfected in vitro. The formulation consists of plasmid DNA adsorbed on to cationic microparticles composed of the biodegradable polymer polylactide-co-glycolide (PLG) and the cationic surfactant, cetyltrimethylammonium bromide (CTAB). Using preparations of fluorescentlabeled plasmid DNA formulated on PLG-CTAB microparticles to study internalization by macrophages and dendritic cells in vitro and in vivo, we found that most, but not all, of

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“…Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be potent antigen delivery systems for the induction of immune responses (10)(11)(12). Microparticles are valuable carriers for the targeting of antigens to APC because they have been demonstrated to be efficiently phagocytosed by DC in vitro (3,13) and in vivo (14).…”

Section: Introductionmentioning

confidence: 99%

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Jilek¹,

Ulrich²,

Merkle³

et al. 2004

Pharm Res

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Purpose. Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be promising carrier systems for vaccine delivery. Here, we have investigated the capacity of different PLA and PLGA microparticle formulations to induce stimulation of human blood monocyte-derived dendritic cells (DCs). Methods. Stimulation of human derived dendritic cells by plain microparticles were compared with microparticles loaded with plasmid DNA or double-stranded salmon DNA either by encapsulation or adsorption to the surface of cationic microparticles. Stimulation of DCs was monitored by the up-regulation of surface maturation markers CD83 and CD86 and the secretion of IL-12 and TNF-␣. Results. Slowly degrading PLA microparticles did not induce any detectable stimulation or activation of DCs. In contrast, fast degrading PLGA microparticles were able to influence DC maturation and cytokine secretion dependent on their surface charge. Anionic PLGA microparticles induced an up-regulation of CD83 and high TNF-␣ secretion, which was further enhanced up to the level of the potent stimulator lipopolysaccharide (LPS) when plasmid DNA was encapsulated. Moreover, the secretion of significant amounts of IL-12 was observed. Cationic PLGA microparticles induced an up-regulation of CD86 and moderate TNF-␣ secretion, but no IL-12 secretion, with no additional effects in the presence of plasmid DNA. Conclusions. The data suggest that the composition and charge of biodegradable DNA-loaded microparticles profoundly influences maturation and cytokine secretion in DCs. Thus, the individual formulation of microparticles used as a vaccine carrier system might considerably influence the profile of the immune response.

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Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses

Cited by 222 publications

References 10 publications

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

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