Synthesis and Characterization of Glycol Chitosan DNA Nanoparticles for Retinal Gene Delivery

Mitra, Riten; Han, Zongchao; Merwin, Miles J.; Taai, Muhammed Al; Conley, Shannon M.; Naash, Muna I.

doi:10.1002/cmdc.201300371

Cited by 46 publications

(35 citation statements)

References 53 publications

(74 reference statements)

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“…Fundus photographs were acquired following our earlier method with Micron III (Phoenix Research laboratories, Pleasanton, CA) imaging system [32,33]. Animals were first anesthetized by intramuscular injection of 85 mg/kg ketamine and 14 mg/kg xylazine (Butler Schein Animal Health, Dublin, OH).…”

Section: Methodsmentioning

confidence: 99%

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

Mitra

Nichols

Guo

et al. 2016

Journal of Controlled Release

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We recently reported that the Ins2Akita mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2Akita mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP). The plasmid was compacted by CK30PEG10K into DNA nanoparticles (NPs) for in vivo delivery. Murine endothelial cell line, SVEC4-10, was first transfected with the plasmid. The mRNA levels of VEGF and VEGFR-2 were quantified by qRT-PCR and showed significant reduction in message expression compared with lipofectamine-transfected cells. Transfection of miR200-b suppressed the migration of SVEC4-10 cells. There was a significant inverse correlation between the level of expression of miR200-b and VEGFR-2. Intravitreal injection of miR200-b DNA NPs significantly reduced protein levels of VEGFR-2 as revealed by western blot and markedly suppressed angiogenesis as evaluated by fundus imaging in aged Ins2Akita mice even after 3 months of post-injection. These findings suggest that NP-mediated miR200-b delivery has negatively regulated VEGFR-2 expression in vivo.

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Section: Methodsmentioning

confidence: 99%

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

Mitra

Nichols

Guo

et al. 2016

Journal of Controlled Release

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“…Transmission electron microscopy (TEM) analysis was carried out as described [30, 31] using one drop of a 1 mM or 5 μM Y 2 O 3 NP (Sigma-Aldrich Inc.) dispersion which was prepared under 10W ultrasonication at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration

Mitra

Merwin

Han

et al. 2014

Free Radical Biology and Medicine

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Photoreceptor (PR) cells are prone to accumulation of reactive oxygen species (ROS) and oxidative stress. An imbalance between the production of ROS and cellular antioxidant defenses contributes to PR degeneration and blindness in many different ocular disease states. Yttrium oxide (Y2O3) nanoparticles (NPs) are excellent free radical scavengers due to their non-stoichiometric crystal defects. Here we utilize a murine light stress model to test the efficacy of Y2O3 NPs (~ 10–14 nm in diameter) in ameliorating retinal oxidative stress-associated degeneration. Our studies demonstrate that intravitreal injections of these NPs at doses ranging from 0.1 μM to 5.0 μM two weeks prior to acute light stress protects PRs from degeneration. This protection is reflected both structurally (i.e. decreased light-associated thinning of the outer nuclear layer) and functionally, i.e. in preservation of scotopic and photopic electroretinogram amplitudes. We also observe preservation of structure and function when NPs are delivered immediately after acute light stress, although the magnitude of the preservation is smaller, and only doses ranging from 1.0 μM to 5.0 μM were effective. We show that the Y2O3 NPs are non-toxic and well-tolerated after intravitreal delivery. Our results suggest that Y2O3 NPs have astonishing antioxidant benefits, and with further exploration, may be an excellent strategy for the treatment of oxidative stress associated with multiple forms of retinal degeneration.

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“…Poloxamer has been reported to enhance the transfection efficiency by minimizing the cell injury due to electric shock [10,11]. Amphiphilic GC, a water-soluble chitosan derivative at physiological pH 7.4, has been widely used in the formulation of anti-cancer drugs, nucleic acid transfection and imaging agents for diagnostic purposes [12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

IR 820 dye encapsulated in polycaprolactone glycol chitosan: Poloxamer blend nanoparticles for photo immunotherapy for breast cancer

Kumar

Srivastava

2015

Materials Science and Engineering: C

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In the present study, we have fabricated biocompatible and biodegradable monodisperse IR 820 encapsulated polycaprolactone (PCL) glycol chitosan (GC): Poloxamer blend nanoparticles (PP-IR NPs) for imaging and effective photo-immunotherapy. IR 820 has been used as an imaging and photothermal agent whereas glycol chitosan (GC) as an immunostimulatory agent. The combination of IR 820, poloxamer, and GC can be used effectively for photoimmunotherapy for cancer, drug-resistant and TNF-α resistant estrogen positive breast cancer. PP-IR NPs are stable in aqueous solution. The uniform size of 100-220 nm with a high zeta value of +38 ± 2 mV led them to accumulate in cancer cells. Laser treatment did not affect the morphology of PP-IR NPs as observed under the transmission electron microscope (TEM). In vitro cytotoxicity studies on MCF-7 cells showed enhanced toxicity upon laser treatment. Further, we validated the cell death by reactive oxygen species (ROS) production. Our studies thus showed that PP-IR NPs are effective in suppressing metastatic cancer as the combinational therapy leads to the formation of apoptotic bodies in MCF-7 cells.

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Synthesis and Characterization of Glycol Chitosan DNA Nanoparticles for Retinal Gene Delivery

Cited by 46 publications

References 53 publications

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration

IR 820 dye encapsulated in polycaprolactone glycol chitosan: Poloxamer blend nanoparticles for photo immunotherapy for breast cancer

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