Immunoadjuvant activity of the nanoparticles’ surface modified with mannan

Haddadi, Azita; Hamdy, Samar; Ghotbi, Zahra; Samuel, John; Lavasanifar, Afsaneh

doi:10.1088/0957-4484/25/35/355101

Cited by 27 publications

(29 citation statements)

References 54 publications

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“…-glucans and mannan are recognized by DCs or macrophages, which activates them [32][33][34]. In addition, curdlan-or mannan-modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles also activated the macrophages or dendritic cells [45,46]. Therefore, we investigated whether carboxylated polysaccharides retain their capability to activate the immunocompetent cells, or not.…”

Section: Activation Of Dcs By Polysaccharide Derivatives and Liposomesmentioning

confidence: 99%

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

et al. 2017

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For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability. For this study, bioactive polysaccharide-based pH-sensitive polymers were constructed to achieve not only cytoplasmic delivery of antigen but also activation of DCs. Curdlan and mannan were used as bioactive polysaccharides because they are known to activate DCs via their respective interactions with Dectin-1 and Dectin-2. Carboxylated curdlan and mannan promoted Th1 cytokine production from DCs, indicating the activation of DCs by these polysaccharide derivatives. These polymer-modified liposomes released their contents at weakly acidic pH and delivered model antigenic proteins into cytosol of DCs. Subcutaneous administration of curdlan derivative-modified or mannan derivative-modified liposomes induced strong antigen-specific immune responses and stronger antitumor effects than those of liposomes modified with dextran derivative. Therefore, bioactive polysaccharide-modified liposomes that achieve both cytoplasmic delivery of antigen and activation of DCs are promising for cancer immunotherapy.

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Section: Activation Of Dcs By Polysaccharide Derivatives and Liposomesmentioning

confidence: 99%

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

et al. 2017

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“…The samples were then placed in a 96-well microplate using a microplate reader at 450 nm (background 570 nm) according to the manufacturer's instructions. 37 The minimum detection levels of the cytokines were 15, 4, 15, and 15 pg/mL for IL-12, IL-6, IFNγ, and TNF-α, respectively.…”

Section: Detection Of Cytokine Secretionmentioning

confidence: 89%

“…37 Lipopolysaccharide (LPS) 1 µg/mL was used as positive control, and an unstimulated cell was used as negative control. NP-DC samples were acquired on a FACS Calibur machine and analyzed using CellQuest Pro software (BD Biosciences).…”

mentioning

confidence: 99%

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

Jahan¹,

Sadat²,

Haddadi³

2018

IJN

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The aim of this research was to develop a targeted antigen–adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.

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“…For example, COOH terminated NPs can result in a slightly acidic environment, that may cause degradation of encapsulated antigen during formulation process or inside endosomal compartment. 9 The present study focuses on the formulation optimization with anti-CD205 ligand using both capped and uncapped PLGA; each type offered with low and high viscosity grades ( Figure 1). 10 Discussions are based on the comparison and evaluation of how different process parameters affect these two subtypes of ester and COOH ended PLGA NPs for in vitro experiment setups.…”

Section: Introductionmentioning

confidence: 99%

Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles

Jahan¹,

Haddadi²

2015

IJN

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The purpose of this study was to assess the effect of various formulation parameters on anti-CD205 antibody decorated poly( d , l -lactide co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to target dendritic cells (DCs). In brief, emulsification solvent evaporation technique was adapted to design NP formulations using two different viscosity grades (low and high) of both ester and carboxylic acid terminated PLGA. Incorporation of ligand was achieved following physical adsorption or chemical conjugation processes. The physicochemical characterizations of formulations were executed to assess the effects of different solvents (chloroform and ethyl acetate), stabilizer percentage, polymer types, polymer viscosities, ligand-NP bonding types, cross-linkers, and cryoprotectants (sucrose and trehalose). Modification of any of these parameters shows significant improvement of physicochemical properties of NPs. Ethyl acetate was the solvent of choice for the formulations to ensure better emulsion formation. Infrared spectroscopy confirmed the presence of anti-CD205 antibody in the NP formulation. Finally, cytotoxicity assay confirmed the safety profile of the NPs for DCs. Thus, ligand modified structurally concealed PLGA NPs is a promising delivery tool for targeting DCs in vivo.

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Immunoadjuvant activity of the nanoparticles’ surface modified with mannan

Cited by 27 publications

References 54 publications

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles

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