Nanomaterial-Mediated Delivery of MLKL Plasmids Sensitizes Tumors to Immunotherapy and Reduces Metastases.

Cancer immunotherapy has emerged as a promising approach for the induction of an antitumor response. While immunotherapy response rates are very high in some cancers, the efficacy against solid tumors remains limited caused by the presence of an immunosuppressive tumor microenvironment. Induction of immunogenic cell death (ICD) in the tumor can be used to boost immunotherapy response in solid cancers by eliciting the release of immune-stimulatory components.

Inorganic Nanoparticles Change Cancer-Cell-Derived Extracellular Vesicle Secretion Levels and Cargo Composition, Resulting in Secondary Biological Effects.

Over the past decades, the medical exploitation of nanotechnology has been largely increasing and finding its way into translational research and clinical applications. Despite their biomedical potential, uncertainties persist regarding the intricate role that nanomaterials may play on altering physiology in healthy and diseased tissues. Extracellular vesicles (EVs) are recognized as an important pathway for intercellular communication and known to be mediators of cellular stress.

The Efficacy of Nanoparticle Delivery to Hypoxic Solid Tumors by ciRGD Co-Administration Depends on Neuropilin-1 and Neutrophil Levels.

The ability to improve nanoparticle delivery to solid tumors is an actively studied domain, where various mechanisms are looked into. In previous work, the authors have looked into nanoparticle size, tumor vessel normalization, and disintegration, and here it is aimed to continue this work by performing an in-depth mechanistic study on the use of ciRGD peptide co-administration. Using a multiparametric approach, it is observed that ciRGD can improve nanoparticle delivery to the tumor itself, but also to tumor cells specifically better than vessel normalization strategies.

Cu-doped TiO nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies.

Nanoparticle-mediated cancer immunotherapy holds great promise, but more efforts are needed to obtain nanoformulations that result in a full scale activation of innate and adaptive immune components that specifically target the tumors. We generated a series of copper-doped TiO nanoparticles in order to tune the kinetics and full extent of Cu ion release from the remnant TiO nanocrystals. Fine-tuning nanoparticle properties resulted in a formulation of 33% Cu-doped TiO which enabled short-lived hyperactivation of dendritic cells and hereby promoted immunotherapy.

Multinucleation resets human macrophages for specialized functions at the expense of their identity.

Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous material. How multinucleation per se contributes to functional specialization of mature mononuclear macrophages remains poorly understood in humans. Here, we integrate comparative transcriptomics with functional assays in purified mature mononuclear and multinucleated human osteoclasts, LGCs and FBGCs.

Gold nanoparticle delivery to solid tumors: a multiparametric study on particle size and the tumor microenvironment.

Nanoparticle (NP) delivery to solid tumors remains an actively studied field, where several recent studies have shed new insights into the underlying mechanisms and the still overall poor efficacy. In the present study, Au NPs of different sizes were used as model systems to address this topic, where delivery of the systemically administered NPs to the tumor as a whole or to tumor cells specifically was examined in view of a broad range of tumor-associated parameters. Using non-invasive imaging combined with histology, immunohistochemistry, single-cell spatial RNA expression and image-based single cell cytometry revealed a size-dependent complex interaction of multiple parameters that promoted tumor and tumor-cell specific NP delivery.

The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors.

Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor.

Role of inorganic nanoparticle degradation in cancer therapy.

Nanomaterials are currently widely exploited for their potential in the development of novel cancer therapies, and so far, mainly nanoparticles (NPs) consisting of liposomes and polymers have made their way into the clinic. However, major bottlenecks for the clinical translation of other types of NPs ( inorganic) are the lack of knowledge concerning their long-term distribution and their potential toxicity. To counter this, various research groups have worked on soluble NPs, such as zinc oxide (ZnO), copper oxide (CuO), and silver (Ag), which tend to dissolve spontaneously into their ionic form, releasing toxic metal ions and leading to reactive oxygen species (ROS) generation when exposed to cellular environments.

A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity.

Despite the progress in nanotechnology for biomedical applications, great efforts are still being employed in optimizing nanoparticle (NP) design parameters to improve functionality and minimize bionanotoxicity. In this study, we developed CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) that are compact ligand-coated and surface-functionalized with an HIV-1-derived TAT cell-penetrating peptide (CPP) analog to improve both biocompatibility and cellular uptake. Multiparametric studies were performed in different mammalian and murine cell lines to compare the effects of varying QD size and number of surface CPPs on cellular uptake, viability, generation of reactive oxygen species, mitochondrial health, cell area, and autophagy.

Tyrosine Kinase Inhibitor Gold Nanoconjugates for the Treatment of Non-Small Cell Lung Cancer.

Gold nanoparticles (AuNPs) have emerged as promising drug delivery candidates that can be leveraged for cancer therapy. Lung cancer (LC) is a heterogeneous disease that imposes a significant burden on society, with an unmet need for new therapies. Chemotherapeutic drugs such as afatinib (Afb), which is clinically approved for the treatment of epidermal growth factor receptor positive LC, is hydrophobic and has low bioavailability leading to spread around the body, causing severe side effects.

Cytotoxicity of prion protein-derived cell-penetrating peptides is modulated by pH but independent of amyloid formation.

Prion diseases are associated with conversion of cellular prion protein (PrP) into an abnormally folded and infectious scrapie isoform (PrP). We previously showed that peptides derived from the unprocessed N-termini of mouse and bovine prion proteins, mPrP and bPrP function as cell-penetrating peptides (CPPs), and destabilize model membrane systems, which could explain the infectivity and toxicity of prion diseases. However, subsequent studies revealed that treatment with mPrP or bPrP significantly reduce PrP levels in prion-infected cells.