A5029815998- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Advanced Polymer Synthesis and Characterization
- Nanoplatforms for cancer theranostics
- SARS-CoV-2 and COVID-19 Research
- Hydrogels: synthesis, properties, applications
- Polymer Surface Interaction Studies
- Aquaculture disease management and microbiota
- biodegradable polymer synthesis and properties
- Pneumonia and Respiratory Infections
- Protein purification and stability
- Dendrimers and Hyperbranched Polymers
- interferon and immune responses
- Extracellular vesicles in disease
- Neonatal Respiratory Health Research
- Microencapsulation and Drying Processes
- Inflammasome and immune disorders
- Supramolecular Self-Assembly in Materials
- Advanced Drug Delivery Systems
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer, Stress, Anesthesia, and Immune Response
- Proteoglycans and glycosaminoglycans research
- MicroRNA in disease regulation
Ghent University
2017-2024
Cornell University
2024
Ghent University Hospital
2017-2023
Cancer Research Institute Ghent
2017-2023
École Polytechnique Fédérale de Lausanne
2021
High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as natural ferroptosis-inducing agent in neuroblastoma, which acts through novel double-edged mechanism. WA dose-dependently either activates the nuclear factor–like 2 pathway targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical induction). Noncanonical induction characterized by an...
The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NPs) flowing in blood to reach tumors by a passive targeting mechanism. Here, using transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NPs extravasate from vasculature granulomas assemble during tuberculosis (TB) infection. PEGylated liposomes other NP cross endothelial barriers near infection sites...
Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from site injection into systemic circulation. Here, we report on design and synthesis an amphiphilic polymer-prodrug conjugate imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures 200 nm. The contains endosomal enzyme-responsive linker enabling degradation...
Abstract The search for vaccines that protect from severe morbidity and mortality because of infection with acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causes disease 2019 (COVID‐19) is a race against clock virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting conjugated to chain end cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It water‐soluble exhibits massive translocation lymph nodes upon local...
Small molecule immuno-modulators such as agonists of Toll-like receptors (TLRs) are attractive compounds to stimulate innate immune cells toward potent antiviral and antitumor responses. However, small molecules rapidly enter the systemic circulation cause "wasted inflammation". Hence, synthetic strategies confine their radius action lymphoid tissue great relevance, both enhance efficacy concomitantly limit toxicity. Here, we demonstrate that covalent conjugation a TLR7/8 agonist...
Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage inherent serum-protein-binding property lipid motifs their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid-polymer conjugates that suppress inflammation but provoke potent lymph-node activation. This work provides a...
Abstract The zebrafish embryo is a vertebrate well suited for visualizing nanoparticles at high resolution in live animals. Its optical transparency and genetic versatility allow noninvasive, real‐time observations of vascular flow their interactions with cells throughout the body. As consequence, this system enables acquisition quantitative data that are difficult to obtain rodents. Until now, few studies using model have only described semiquantitative results on key nanoparticle...
Abstract Targeting the stimulator of interferon genes (STING) pathway with cyclic dinucleotides (CDNs), natural STING agonists, is a promising immunotherapeutic strategy for cancer. However, clinical application CDNs as therapeutics greatly hindered by their intrinsic properties including negative charges, small molecular weight, and high susceptibility to enzymatic degradation. Mn 2+ ions have been recently discovered directly activate GMP‐AMP (cGAMP) synthase (cGAS) augment cGAMP‐STING...
Abstract Degradable synthetic crosslinking is a versatile strategy to harness nanomaterials against disassembly in complex physiological medium prompted by dilution effects or competitive interaction. In particular, chemical bonds such as ketals that are stable at conditions but cleaved response disease‐mediated intracellular (e.g., mildly acidic pH) of great relevance for biomedical applications. Despite the range spectroscopic chromatographic analyses methods allow degradation solution be...
Abstract Interactive materials that can respond to a trigger by changing their morphology, but also gradually degrade into fully soluble state, are attractive building blocks for the next generation of biomaterials. Herein, we design such transiently responsive polymers exhibit UCST behaviour while losing this property in response hydrolysis reaction polymer side chains. The operate within physiologically relevant window terms temperature, pH, and ionic strength. Whereas has been reported...
Immune stimulatory antibodies and cytokines elicit potent antitumor immunity. However, the dose-limiting systemic toxicity greatly hinders their clinical applications. Here, we demonstrate a chemical approach, termed “switchable” immune modulator (Sw-IM), to limit exposure therefore ameliorate toxicities. Sw-IM is biomacromolecular therapeutic reversibly masked by biocompatible polymers through linkers that are responsive tumor-specific stimuli, such as high reducing potential acidic pH....
Despite their great versatility and ease of functionalization, most polymer-based nanocarriers intended for use in drug delivery often face serious limitations that can prevent clinical translation, such as uncontrolled release off-target toxicity, which mainly originate from the burst phenomenon. In addition, residual solvents formulation process induce alter physico-chemical biological properties strongly impair further pharmaceutical development. To address these issues, we report polymer...
Peptide-based subunit vaccines are attractive in view of personalized cancer vaccination with neo-antigens, as well for the design newest generation against infectious diseases. Key to mounting robust antigen-specific immunity is delivery antigen antigen-presenting (innate immune) cells lymphoid tissue concomitant innate immune activation promote presentation T and shape amplitude nature response. Nanoparticles that co-deliver both peptide molecular adjuvants suited this task. However,...
Nanoparticle conjugation is a powerful method to reduce the side effects of anticancer agents such as doxorubicin by altering pharmacokinetic profile drug. Nanoparticles can prolong circulation time and could also promote enhanced accumulation in tumors, either passively via permeability retention effect or actively when decorated with targeting motifs. For particular case doxorubicin, hydrazone-based chemistry popular but commonly involves laborious chemical transformation steps. Here, we...
Abstract In situ anti‐tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens T in lymphoid tissue. Here, a multifunctional nanocomplex based calcium crosslinked polyaspartic acid conjugated either toll‐like receptor (TLR)7/8 agonist or photosensitizer reported. Intratumoral administration followed by laser irradiation induces cell killing hence generation pool...
Abstract Pharmacological strategies to activate innate immune cells are of great relevance in the context vaccine design and anticancer therapy, mount broad responses able clear infection malignant cells. Synthetic CpG oligodeoxynucleotides (CpG‐ODNs) short single‐stranded DNA molecules containing unmethylated dinucleotides a phosphorothioate backbone. Class B ODNs robust through TLR9‐dependent NF‐κB signaling pathway. This feature is attractive exploit cancer immunotherapy. Soluble CpG‐ODNs...
Pharmacokinetics of active substances and their biodistribution profiles are crucial aspects for safe successful administration. Since many immunogenic compounds do not meet all requirements effective administrations,...
The quest for new potent and safe adjuvants with which to skew boost the immune response of vaccines against intracellular pathogens cancer has led discovery a series small molecules that can activate Toll-like receptors (TLRs). Whereas many molecule TLR agonists cope problematic safety profile, amphotericin B (AmpB), Food Drug Administration approved antifungal drug, recently been discovered possess TLR-triggering activity. However, its poor aqueous solubility cytotoxicity at elevated...
Nanogels show long <italic>in vivo</italic> blood circulation time and high tumor accumulation.
Strategies that can reduce the harmful side effects of potent immunomodulatory drugs are in high demand to facilitate clinical translation newest generation immunotherapy. Indeed, uncontrolled triggering immune system lead life-threatening cascade reactions, such as e.g. cytokine storm. In particular, drug formulations combine simplicity and degradability formidable relevance. Imidazoquinolines an excellent example small molecule exhibit unformulated form a highly undesirable pharmacokinetic...