Intratumoral delivery of 4-1BBL boosts IL-12-triggered anti-glioma immunity.

The standard of care in high-grade gliomas has remained unchanged in the past 20 years. Efforts to replicate effective immunotherapies in non-cranial tumors have led to only modest therapeutical improvements for patients with glioma. Here, we demonstrate that intratumoral (i.

Intratumoral gene delivery of 4-1BBL boosts IL-12-triggered anti-glioblastoma immunity.

The standard of care in high-grade gliomas has remained unchanged in the past 20 years. Efforts to replicate effective immunotherapies in non-cranial tumors have led to only modest therapeutical improvements in glioblastoma (GB). Here, we demonstrate that intratumoral administration of recombinant interleukin-12 (rIL-12) promotes local cytotoxic CD8 T cell accumulation and conversion into an effector-like state, resulting in a dose-dependent survival benefit in preclinical GB mouse models.

Enhanced mRNA delivery using ultrasound-delivered click reactive anchors.

Therapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with transcyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), yielding ACRA-TCO and ACRA-mTz.

Pro-inflammatory and genotoxic responses by metal oxide nanomaterials in alveolar epithelial cells and macrophages in submerged condition and air-liquid interface: An in vitro-in vivo correlation study.

Studies on in vitro-in vivo correlations of inflammatory and genotoxic responses are needed to advance new approach methodologies. Here, we assessed pro-inflammatory and genotoxic responses by 13 nanosized metal oxides (nMeOx) and quartz (DQ12) in alveolar epithelial cells (A549) and macrophages (THP-1a) exposed in submerged conditions, and in A549:THP-1a co-cultures in air-liquid interface (ALI) system. Soluble nMeOx produced the highest IL-8 expression in A549 and THP-1a cells in submerged conditions (≥2-fold, p < 0.

Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.

Gene editing technologies have the potential to correct genetic disorders by modifying, inserting, or deleting specific DNA sequences or genes, paving the way for a new class of genetic therapies. While gene editing tools continue to be improved to increase their precision and efficiency, the limited efficacy of in vivo delivery remains a major hurdle for clinical use. An ideal delivery vehicle should be able to target a sufficient number of diseased cells in a transient time window to maximize on-target editing and mitigate off-target events and immunogenicity.

Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives.

Animal experiments are highly relevant models for the assessment of toxicological effects of engineered nanomaterials (ENMs), due to lack of biomonitoring and epidemiological studies. However, the expanding number of ENMs with different physico-chemical properties strains this approach, as there are ethical concerns and economical challenges with the use of animals in toxicology. There is an urgent need for cell culture models that predict the level of toxicological responses in vivo, consequently reducing or replacing the use of animals in nanotoxicology.

Systematic review on primary and secondary genotoxicity of carbon black nanoparticles in mammalian cells and animals.

Carbon black exposure causes oxidative stress, inflammation and genotoxicity. The objective of this systematic review was to assess the contributions of primary (i.e.

Assessment of primary and inflammation-driven genotoxicity of carbon black nanoparticles and .

Carbon black nanoparticles (CBNPs) have a large surface area/volume ratio and are known to generate oxidative stress and inflammation that may result in genotoxicity and cancer. Here, we evaluated the primary and inflammatory response-driven (i.e.

Grouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation: a case-study.

Background: The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential.

Genotoxicity of multi-walled carbon nanotube reference materials in mammalian cells and animals.

Carbon nanotubes (CNTs) were the first nanomaterials to be evaluated by the International Agency for Research on Cancer (IARC). The categorization as possibly carcinogenic agent to humans was only applicable to multi-walled carbon nanotubes called MWCNT-7. Other types of CNTs were not classifiable because of missing data and it was not possible to pinpoint unique CNT characteristics that cause cancer.

Pro-inflammatory response and genotoxicity caused by clay and graphene nanomaterials in A549 and THP-1 cells.

Nanoclays and graphene oxide nanomaterials represent a class of materials sharing similar shapes constituted of high aspect ratio platelets. The increased production of these materials for various industrial applications increases the risk of occupational exposure, consequently with elevated risk of adverse reactions and development of pulmonary diseases, including lung cancer. In this study, pro-inflammatory responses and genotoxicity were assessed in alveolar epithelial cells (A549) and activated THP-1 macrophages (THP-1a) after exposure to three nanoclays; a pristine (Bentonite) and two surface modified (benzalkonium chloride-coated Nanofil9, and dialkyldimethyl-ammonium-coated NanofilSE3000); graphene oxide (GO) and reduced graphene oxide (r-GO) nanomaterials.

In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT.

Background: Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data.

Reactive oxygen species production, genotoxicity and telomere length in FE1-Muta™Mouse lung epithelial cells exposed to carbon nanotubes.

Carbon nanotubes (CNTs) are fiber-like nanomaterials, which are used in various applications with possible exposure to humans. The genotoxicity and carcinogenic potential of CNTs remain to be fully understood. This study assessed the genotoxicity of three different multi-walled carbon nanotubes (MWCNTs) (MWCNT-7, NM-401 and NM-403) and one single-walled carbon nanotube (SWCNT) (NM-411) in FE1-Muta™Mouse lung epithelial (MML) cells using the alkaline comet assay.

Organomodified nanoclays induce less inflammation, acute phase response, and genotoxicity than pristine nanoclays in mice lungs.

Surface modification by different quaternary ammonium compounds (QAC) makes nanoclays more compatible with various polymeric matrices, thereby expanding their potential applications. The growing industrial use of nanoclays could potentially pose a health risk for workers. Here, we assessed how surface modification of nanoclays modulates their pulmonary toxicity.