Macrophage mannose receptor-specific gene delivery vehicle for macrophage engineering

Ruan, Gui‐Xin; Chen, Yu-Zhe; Yao, Xinglei; Du, Anariwa; Tang, Guping; Shen, Youqing; Tabata, Yasuhiko

doi:10.1016/j.actbio.2014.01.012

Cited by 38 publications

(36 citation statements)

References 50 publications

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“…D-mannose leads to a local anti-inflammatory phenotype similar to that observed in M2 activated immune cells that may only be important during the period of sensitization for efficient non-viral transgene phagocytosis. Indeed, a recent report engineered a mannose-specific targeted non-viral gene delivery method that resulted in superior gene expression in macrophage cell lines [80]. The data reported here show, for the first time, that a previously demonstrated ineffective low dose of non-viral pDNA-IL-10 (1 μg) gene therapy [87] is now efficacious for over three weeks when delivered with mannose upon a single i.t.…”

Section: Discussionmentioning

confidence: 72%

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Improvement of spinal non-viral IL-10gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain

Dengler

Alberti

Bowman

et al. 2014

J Neuroinflammation

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BackgroundPeri-spinal subarachnoid (intrathecal; i.t.) injection of non-viral naked plasmid DNA encoding the anti-inflammatory cytokine, IL-10 (pDNA-IL-10) suppresses chronic neuropathic pain in animal models. However, two sequential i.t. pDNA injections are required within a discrete 5 to 72-hour period for prolonged efficacy. Previous reports identified phagocytic immune cells present in the peri-spinal milieu surrounding the i.t injection site that may play a role in transgene uptake resulting in subsequent IL-10 transgene expression.MethodsIn the present study, we aimed to examine whether factors known to induce pro-phagocytic anti-inflammatory properties of immune cells improve i.t. IL-10 transgene uptake using reduced naked pDNA-IL-10 doses previously determined ineffective. Both the synthetic glucocorticoid, dexamethasone, and the hexose sugar, D-mannose, were factors examined that could optimize i.t. pDNA-IL-10 uptake leading to enduring suppression of neuropathic pain as assessed by light touch sensitivity of the rat hindpaw (allodynia).ResultsCompared to dexamethasone, i.t. mannose pretreatment significantly and dose-dependently prolonged pDNA-IL-10 pain suppressive effects, reduced spinal IL-1β and enhanced spinal and dorsal root ganglia IL-10 immunoreactivity. Macrophages exposed to D-mannose revealed reduced proinflammatory TNF-α, IL-1β, and nitric oxide, and increased IL-10 protein release, while IL-4 revealed no improvement in transgene uptake. Separately, D-mannose dramatically increased pDNA-derived IL-10 protein release in culture supernatants. Lastly, a single i.t. co-injection of mannose with a 25-fold lower pDNA-IL-10 dose produced prolonged pain suppression in neuropathic rats.ConclusionsPeri-spinal treatment with D-mannose may optimize naked pDNA-IL-10 transgene uptake for suppression of allodynia, and is a novel approach to tune spinal immune cells toward pro-phagocytic phenotype for improved non-viral gene therapy.

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Section: Discussionmentioning

confidence: 72%

“…Second, the spinal anti-inflammatory effects of D-mannose may be critical for inducing enhanced phagocytosis thereby optimizing naked pDNA-IL-10 uptake. Indeed, recent evidence supports effective mannose receptor-mediated non-viral gene delivery as superior to currently available transfectant reagents [80,81]. …”

Section: Discussionmentioning

confidence: 99%

Improvement of spinal non-viral IL-10gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain

Dengler

Alberti

Bowman

et al. 2014

J Neuroinflammation

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“…). Previous studies have shown mannosylated polymers to undergo receptor‐mediated endocytosis, which accumulate in endosomes . Therefore, higher TGDP of m‐PEI polymers can be explained on the basis of improved targeting via mannose receptor.…”

Section: Resultsmentioning

confidence: 98%

Bimodal Targeting Using Sulfonated, Mannosylated PEI for Combined Gene Delivery and Photodynamic Therapy

Chitgupi

Chen

et al. 2017

Photochem & Photobiology

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Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT. Polymers libraries were created that consisted of cationic polyethyleneimine (PEI) conjugated to the photosensitizer pyropheophorbide-α, with sulfonation (to target selectin-expressing cells) and mannosylation (to target TAMs). Polyplexes, consisting of these polymers electrostatically bound to DNA, were analyzed for transfection efficacy and cytotoxicity towards epithelial cells and macrophages to assess dual-targeting. This study provides preliminary proof of principle for using modified PEI for targeted gene delivery and PDT.

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“…For example, a cationic mannan-spermine copolymer was engineered for complexation of a model pDNA (pGL3), and the transfection efficiency was tested in a panel of immortalised cell lines, including macrophage and dendritic cells. The results showed high transfection levels in macrophages, which were associated to the receptor-mediated internalization of the mannan complexes (Ruan et al, 2014).…”

Section: Nucleic Acid-based Nanovaccinesmentioning

confidence: 95%

“…Nanoengineering of nucleic acids with mannan has been mainly achieved through the synthesis of cationic derivatives of mannan (Lu et al, 2007;Ruan et al, 2014;Tang et al, 2008Tang et al, , 2009. For example, a cationic mannan-spermine copolymer was engineered for complexation of a model pDNA (pGL3), and the transfection efficiency was tested in a panel of immortalised cell lines, including macrophage and dendritic cells.…”

Section: Nucleic Acid-based Nanovaccinesmentioning

confidence: 99%

Nanoengineering of vaccines using natural polysaccharides

Cordeiro

Alonso

Fuente

2015

Biotechnology Advances

102

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Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers.

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Macrophage mannose receptor-specific gene delivery vehicle for macrophage engineering

Cited by 38 publications

References 50 publications

Improvement of spinal non-viral IL-10gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain

Improvement of spinal non-viral IL-10gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain

Bimodal Targeting Using Sulfonated, Mannosylated PEI for Combined Gene Delivery and Photodynamic Therapy

Nanoengineering of vaccines using natural polysaccharides

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