Virus-like nanostructures for tuning immune response

Mammadov, Rashad; Çınar, Göksu; Gündüz, Nuray; Göktas, Melis; Kayhan, Handan; Tohumeken, Şehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibaşı, Tuncay; Dâna, Aykutlu; İde, Semra; Tekinay, Ayşe B.; Güler, Mustafa O.

doi:10.1038/srep16728

Cited by 40 publications

(34 citation statements)

References 50 publications

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“…Vaccine delivery is the presentation of target antigens to the immune system in order to elicit immune responses appropriate for protection against a specific disease. One of the approaches is based on mimicking natural pathogens as viruses and prompting first the innate response and then the adaptive immune response [33]. …”

Section: Discussionmentioning

confidence: 99%

Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis

Costa

Righelli

Russo

et al. 2017

IJMS

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Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.

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Section: Discussionmentioning

confidence: 99%

Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis

Costa

Righelli

Russo

et al. 2017

IJMS

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“…Lynn et al attached small‐molecule TLR‐7/8a agonists to hydrophilic polymers to form polymer‐TLR‐7/8a conjugates by “grafting to” strategy . Recently, inspired by quinone chemistry, we have also introduced “thiol‐quinone” reaction to attach thiolated CpG to NPs for fabricating pathogen‐mimetic adjuvants by the “grafting to” method . Besides, few works employ multicomponent strategy to design adjuvants.…”

Section: Methodsmentioning

confidence: 99%

One‐Pot, Multicomponent Strategy for Designing Lymphoseek‐Inspired Hetero‐Glycoadjuvant@AuNPs

Liu

Wen

Shen

et al. 2019

Macromol. Rapid Commun.

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transported to draining lymph nodes. The second approach is based on the activation of antigen-presenting cells (APCs) to induce T cell. [9,10] Recently, inspired by the lymphoseek [11] (which is a mannose-conjugated, dextran-based LN imaging agent, acting as receptor-targeted radiotracer in breast cancer and melanoma patients), we have first developed LN-targeting adjuvant by conjugating toll-like receptor (TLR) [9] agonists, unmethylated Cytosinephosphate-Guanosine (CpG) to natural dextran. [12] Although dextran-functionalized adjuvant could not increase adjuvant internalization, they could distinctly enhance CD8 + T-cell responses, and improve cancer immunotherapy. [12] More importantly, dextran-based adjuvants could not only activate tumor-specific CTL responses, but also inhibit myeloid-derived suppressor cells (MDSCs) in tumor immune microenvironment. [13] Many works indicate that binding between C-type lectin receptors (CLRs) and carbohydrate ligands [14][15][16][17][18][19] is important not only for the induction of T-cell responses, but also for the inhibition of immunosuppressive microenvironment. [13] Therefore, lymphoseek-inspired vaccine should have advantages of promoting vaccine internalization, potentiating CD8 + T-cell responses and reducing the immunosuppressive activity, and become a promising candidate for nextgeneration cancer vaccine.Much effort has been devoted to developing new methodologies for the design and preparation of multifunctional adjuvant, which is the most challenging work. To obtain bioactive adjuvant, simple and highly efficient reaction should be used to formulate adjuvant. To date, most of the works use "grafting to" method to generate target adjuvant. [20][21][22][23] Lynn et al. attached small-molecule TLR-7/8a agonists to hydrophilic polymers to form polymer-TLR-7/8a conjugates by "grafting to" strategy. [24] Recently, inspired by quinone chemistry, we have also introduced "thiol-quinone" reaction to attach thiolated CpG to NPs for fabricating pathogen-mimetic [25][26][27] adjuvants by the "grafting to" method. [28] Besides, few works employ multicomponent strategy to design adjuvants. It is well known that onepot multicomponent strategy offers obvious advantages of simplicity and high efficiency over traditional chemical reactions. Moreover, one-pot strategy is more convenient to obtain high concentration adjuvants. Herein, we report a novel multicomponent strategy to develop lymphoseek-inspired adjuvants in one-pot. First, photo-induced reversible addition-fragmentation Glycoadjuvants Searching for vaccines (antigen and adjuvant) with easy preparation and strong T-cell response are crucial for antitumor immunity. In this work, to design lymphoseek-inspired vaccine possessing the abilities of promoting vaccine internalization and enhancing CD8 + T-cell responses, a simple multicomponent strategy is successfully utilized to fabricate lymph node and dendritic cell dual-targeting glycoadjuvant@AuNPs in one pot, where three different components, catechol-containing glycopol...

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“…13 The PA assemblies provide structural organization for delivery of both hydrophobic and hydrophilic therapeutic moieties, which can be modulated through the design of building blocks. 7,[14][15][16] Moreover, targeted high efficacy delivery of small therapeutics can be achieved through functionalization of PA nano-structures with ligand-binding, cell-penetrating and internalization-associated peptide sequences. 17,18 Biocompatibility and biodegradability of the PA assemblies through different proteases [19][20][21] also enhance their utility as delivery architectures, especially for chemotherapeutics that show high cytotoxicity when administered directly to the blood stream.…”

Section: Introductionmentioning

confidence: 99%

Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels

et al. 2017

Self Cite

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Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.

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Virus-like nanostructures for tuning immune response

Cited by 40 publications

References 50 publications

Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis

Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis

One‐Pot, Multicomponent Strategy for Designing Lymphoseek‐Inspired Hetero‐Glycoadjuvant@AuNPs

Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels

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