Glycodendrimers as functional antigens and antitumor vaccines

Shiao, Tze Chieh; Roy, René

doi:10.1039/c2nj20873c

Cited by 88 publications

(60 citation statements)

References 88 publications

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“…Potentially, these nanoparticles can be successfully used not only as vectors of targeted delivery of drugs to cancer cells, but also as stimulants to augment the anti-tumor attack of the innate immune system. This mild adjuvant-like effect of glycodendrimers was previously mentioned in the study on their use in facilitating anti-tumor vaccine application, but no molecular mechanism was proposed (40). …”

Section: Discussionmentioning

confidence: 88%

Sugar-Modified Poly(propylene imine) Dendrimers Stimulate the NF-κB Pathway in a Myeloid Cell Line

et al. 2016

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PurposeFourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors.MethodsTo estimate the cytotoxicity of dendrimers the reasazurin assay was performed. The expression level of NF-κB targets: IGFBP3, TNFAIP3 and TNF was determined by quantitative real-time RT-PCR. Measurement of NF-κB p65 translocation from cytoplasm to nucleus was conducted with a high-content screening platform and binding of NF-κB to a consensus DNA probe was determined by electrophoretic mobility shift assay. The cytokine assay was performed to measure protein concentration of TNFalpha and IL-4.ResultsWe found that PPI-m DS did not impact THP-1 viability and growth even at high concentrations (up to 100 μM). They also did not induce expression of genes for important signaling pathways: Jak/STAT, Keap1/Nrf2 and ER stress. However, high concentrations of 4th generation PPI-m DS (25–100 μM), but not their 3rd generation counterparts, induced nuclear translocation of p65 NF-κB protein and its DNA-binding activity, leading to NF-κB-dependent increased expression of mRNA for NF-κB targets: IGFBP3, TNFAIP3 and TNF. However, no increase in pro-inflammatory cytokine secretion was detected.ConclusionWe conclude that maltose-modified PPI dendrimers of specific size could exert a modest immunomodulatory effect, which may be advantageous in clinical applications (e.g. adjuvant effect in anti-cancer vaccines).

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Section: Discussionmentioning

confidence: 88%

Sugar-Modified Poly(propylene imine) Dendrimers Stimulate the NF-κB Pathway in a Myeloid Cell Line

et al. 2016

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“…Following the same approach, BSA-conjugated vaccines (4) have been prepared with various divalent combinations of sialylated and unsialylated antigens (Fig. 14.4).…”

Section: Protein Carriersmentioning

confidence: 99%

Synthetic Vaccines against Cancers

Fiore¹,

Thomas²,

Daskhan³

et al. 2015

Carbohydrate Chemistry: State of the Art and Challenges for Drug Development

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“…27 Screening of the library by adding concanavalin A (Con A), an aMan specific lectin, to the equilibrating mixture of library components did not evidenced significant differences in the binding affinity within the heterodimer series (Scheme 3). A second family of dynamic carbohydrate libraries was generated from a pool of carbohydrate aldehydes (16)(17)(18)(19)(20)(21) and di-or tritopic hydrazide components (A-H) through reversible acylhydrazone exchange (Scheme 4). 28 The library members can thus incorporate up to three different glycotopes (e.g.…”

Section: (A) ''Shuffled'' Heteroglycoconjugatesmentioning

confidence: 99%

“…[4][5][6][7][8] Synthetic polyconjugates with welldefined structures have contributed to unravel the mechanisms at work, [9][10][11][12] leading eventually to useful tools for biotechnological 13,14 or therapeutic purposes. 15 Typically, these systems incorporate several copies of identical sugar motifs attached to an appropriate scaffold (molecular, dendritic, polymeric) 10,11,[16][17][18] or self-assembled in supramolecular constructs (nanoparticles, vesicles, microarrays). 11,19 It has been amply demonstrated that ligand multivalency increases protein-binding avidities dramatically.…”

Section: Introductionmentioning

confidence: 99%

Multivalency in heterogeneous glycoenvironments: hetero-glycoclusters, -glycopolymers and -glycoassemblies

2013

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Despite efficiently imitating functional ligand presentations in terms of valency and density, most of the reported multivalent carbohydrate prototypes barely reflect the inherent heterogeneity of biological systems, therefore underestimating the potential contribution of synergistic or antagonistic effects to molecular recognition events. To address this question, the design of novel molecular and supramolecular entities displaying different saccharide motifs in a controlled manner is of critical importance. In this review we highlight the current efforts made to synthesize heteromultivalent glycosystems on different platforms (peptides, dendrimers, polymers, oligonucleotides, calixarenes, cyclodextrins, microarrays, vesicles) and to evaluate the influence of heterogeneity in carbohydrateprotein (lectin, antibody) recognition phenomena. Although the number of publications on this topic is limited as compared to the huge volume of reports on homomultivalent sugar displays, the current body of results has already unravelled the existence of new binding mechanisms that operate in heterogeneous environments whose exact biological significance remains to be unveiled.

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Glycodendrimers as functional antigens and antitumor vaccines

Cited by 88 publications

References 88 publications

Sugar-Modified Poly(propylene imine) Dendrimers Stimulate the NF-κB Pathway in a Myeloid Cell Line

Sugar-Modified Poly(propylene imine) Dendrimers Stimulate the NF-κB Pathway in a Myeloid Cell Line

Synthetic Vaccines against Cancers

Multivalency in heterogeneous glycoenvironments: hetero-glycoclusters, -glycopolymers and -glycoassemblies

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