Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants

Lu, Fangjia; Mencia, A. S.; Bi, Lin; Taylor, Alasdair; Yao, Yuan; HogenEsch, Harm

doi:10.1016/j.jconrel.2015.03.002

Cited by 84 publications

(87 citation statements)

References 31 publications

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“…Chemically modified phytoglycogen nanoparticles have been applied as vaccine adjuvants, when combined with different protein antigens. For example, Lu et al reported the synthesis of Nano‐11, phytoglycogen nanoparticles that were modified with octenyl succinic anhydride (forming phytoglycogen octenyl succinate) and (3‐chloro‐2‐hydroxypropyl)‐trimethylammonium chloride ( Figure A). The octenyl succinate groups confer hydrophobicity and negative charges, whereas the quaternary ammonium groups provide positive charges to form a complex with negatively charged ovalbumin, OVA.…”

Section: Glycogen As a Building Block Of Nanostructured Materialsmentioning

confidence: 99%

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Glycogen as a Building Block for Advanced Biological Materials

2019

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complex drug delivery systems that are challenging to scale up and therefore have limited clinical and commercial translation. Although numerous nanoparticles have been widely developed and used for various applications, including biomedical applications, [2] there is a growing interest in nontoxic and degradable alternatives to first-generation synthetic nanomaterials. Ideally the synthesis of such nanoparticles needs to be cost effective, simple, green, reproducible, scalable, and the constitutive building blocks of the nanoparticles should be nontoxic, functional, biodegradable, and available on a large scale. Naturally occurring nanoparticles could be such a valid alternative. These nanoparticles include intracellular structures, such as magnetosomes [3] and glycogen, and extracellular assemblies such as lipoproteins and viruses. [3] Among these, glycogen is the most abundant and versatile biological nanoparticle, which fulfils the requirements for the fabrication of nanostructured biomaterials. Glycogen is nature's prime nanoparticle that exists in most organisms, from bacteria and archaea to humans, [4,5] as a vital component of the cellular energy machinery. It is a highly branched polysaccharide comprising repeating units of glucose connected by linear α-d-(1,4) glycosidic linkages with α-d-(1,6) branching, structured into roughly spherical nanoparticles that have a high water solubility and molecular weight.The use of polysaccharides as components for advanced materials has been an attractive concept for decades. [6,7] A key motive is that polysaccharides, as a natural biomaterial, are endowed with a level of biodegradability and biocompatibility. In addition, they can be easily modified chemically or biochemically to produce functional derivatives, which are important for various therapeutic applications. [8] The structures of polysaccharides vary considerably but span from linear to highly branched polymers with molecular weights ranging from thousands to millions, composed of mono-or disaccharides, or short-chain oligomers bound together by glycosidic linkages. [9] There is a rich history of research on the use of polysaccharides in a range of therapeutic applications including: i) soft tissue engineering, [10,11] where the materials can be designed to mimic the mechanical properties of the extracellular matrix in the tissue; ii) as drug, protein, or gene delivery systems, [7,12,13] where polysaccharides have a large number of reactive groups [14] that allow for tunable properties [12] such as pH-responsiveness; [15] and iii) as nanoprobes for cellular Biological nanoparticles found in living systems possess distinct molecular architectures and diverse functions. Glycogen is a unique biological polysaccharide nanoparticle fabricated by nature through a bottom-up approach. The biocatalytic synthesis of glycogen has evolved over time to form a nanometer-sized dendrimer-like structure (20-150 nm) with a highly branched surface and a dense core. This makes glycogen markedly different from other natur...

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Section: Glycogen As a Building Block Of Nanostructured Materialsmentioning

confidence: 99%

“…A) Schematic describing the preparation of Nano‐11 (phytoglycogen‐octenyl succinate‐(3‐chloro‐2‐hydroxypropyl)‐trimethylammonium chloride, PG‐OS‐CHPTAC) from phytoglycogen. Reproduced with permission . Copyright 2015, Elsevier.…”

Section: Glycogen As a Building Block Of Nanostructured Materialsmentioning

confidence: 99%

Glycogen as a Building Block for Advanced Biological Materials

2019

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“…Due to the relative ease in modifying their chemistries, ESG and similar branched dendrites have the potential to be developed as in vivo therapeutic delivery systems for a variety of cargo. For instance, phytoglycogen has been modified with octenyl succinate to introduce anionic charges and hydrophobicity, enabling the delivery of antigen-vaccines 17 and improved efficacy of the antimicrobial peptide nisin. 18 An area of interest to our group is the cationic modification of ESG to facilitate electrostatic binding and delivery of nucleic acids and small therapeutic molecules to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery

2015

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Nanostructured starches are naturally derived nanomaterials that can be chemically modified to allow for the introduction of functional groups, enhancing their potential for drug delivery and other biotechnology applications. In this proof of concept study, we investigate chemically modified, enzymatically synthesized glycogen (ESG) nanodendrites as a biodegradable, biocompatible, siRNA delivery system. Commercially available ESG was modified using glycidyltrimethylammonium chloride (GTMA), introducing quaternary ammonium groups via an epoxide ring opening reaction. This cationic ESG (cESG) electrostatically bound siRNA and successfully knocked-down protein expression in an in vitro ovarian clear cell carcinoma model. The construct exhibited sustained siRNA delivery for up to six days while exhibiting less toxicity than a common liposome-based siRNA delivery reagent, Lipofectamine RNAiMAX. These promising results set the stage for use of dendritic starch as a cost-effective, easily modifiable nanoscale delivery system for a diverse range of cargo including nucleic acids and therapeutic compounds.

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“…Interferon gamma (IFN-c) and IL4 levels were measured in the collected supernatants by commercially available sandwich-based ELISA kits (R&D Systems Inc., Minneapolis, MN) as described in the kit manual. All tests were performed in duplicate and the mean was recorded for each set of samples (Lu et al 2015).…”

Section: Ifn-c and Il4 Cytokine Detectionmentioning

confidence: 99%

Conjugated anionic PEG-citrate G2 dendrimer with multi-epitopic HIV-1 vaccine candidate enhance the cellular immune responses in mice

Abdoli

Radmehr

Bolhassani

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Multi-epitope vaccines might cause immunity against multiple antigenic targets. Four immunodominant epitopes of HIV-1 genome were used to construct a polytope vaccine, formulated by dendrimer. Two regimens of polytopes mixture with dendrimer were utilized to immunize BALB/c mice. Adjuvants were also used to boost immune responses. The conjugated polytope could arouse significant cellular immune responses (P < 0.05) and Th1 response showed higher intensity compared to Th2 (P < 0.05). Our study depicted that conjugated dendrimer with multi-epitopic rHIVtop4 would efficiently induce cell-mediated immune responses and might be considered as promising delivery system for vaccines formulation.

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Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants

Cited by 84 publications

References 31 publications

Glycogen as a Building Block for Advanced Biological Materials

Glycogen as a Building Block for Advanced Biological Materials

Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery

Conjugated anionic PEG-citrate G2 dendrimer with multi-epitopic HIV-1 vaccine candidate enhance the cellular immune responses in mice

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