Nanomaterials Trigger Functional Anti-Tumoral Responses in Primary Human Immune Cells.

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications are characterized.

Reinforced Polymer-Nanoparticle Hydrogels for Subcutaneous and Sustained Delivery of Trastuzumab.

In oncology, the advent of monoclonal antibody (mAb) therapeutics represents a breakthrough in various cancer diseases. However, these therapies often necessitate iterative hospital visits for intravenous infusion that alter patient quality of life and contribute to the chronic saturation of hospitals. Subcutaneous formulations of mAbs offer a promising alternative facilitating faster administration compared with traditional intravenous methods, while still maintaining the same dosing schedule and providing time-saving advantages.

Spacer engineering in nanoparticle-peptide conjugates boosts targeting specificity for tumor-associated antigens.

Developing and synthesizing nano-objects capable of enabling early targeted diagnosis and ensuring effective tumor treatment represents a significant challenge in the theranostic field. Among various nanoparticles (NPs), iron oxide nanoparticles (IONPs) have made significant contributions to advancing this field. However, a key challenge lies in achieving selective recognition of specific cell types.

Defects or no defects? Or how to design 20-25 nm spherical iron oxide nanoparticles to harness both magnetic hyperthermia and photothermia.

Designing iron oxide nanoparticles (IONPs) to effectively combine magnetic hyperthermia (MH) and photothermia (PTT) in one IONP formulation presents a significant challenge to ensure a multimodal therapy allowing the adaptation of the treatment to each patient. Recent research has highlighted the influence of factors such as the size, shape, and amount of defects on both therapeutic approaches. In this study, 20-25 nm spherical IONPs with a spinel composition were synthesized by adapting the protocol of the thermal decomposition method to control the amount of defects.

Landscape of Subcutaneous Administration Strategies for Monoclonal Antibodies in Oncology.

In recent decades, subcutaneous (SC) administration of monoclonal antibodies (mAbs) has emerged as a promising alternative to intravenous delivery in oncology, offering comparable therapeutic efficacy while addressing patient preferences. This perspective article provides an in-depth analysis of the technological landscape surrounding SC mAb administration in oncology. It outlines various technologies under evaluation across developmental stages, spanning from preclinical investigations to the integration of established methodologies in clinical practice.

Supramolecular Heterodimer Peptides Assembly for Nanoparticles Functionalization.

Nanoparticle (NP) surface functionalization with proteins, including monoclonal antibodies (mAbs), mAb fragments, and various peptides, has emerged as a promising strategy to enhance tumor targeting specificity and immune cell interaction. However, these methods often rely on complex chemistry and suffer from batch-dependent outcomes, primarily due to limited control over the protein orientation and quantity on NP surfaces. To address these challenges, a novel approach based on the supramolecular assembly of two peptides is presented to create a heterotetramer displaying VHs on NP surfaces.

Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb.

Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies.

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs).

3D single cell migration driven by temporal correlation between oscillating force dipoles.

Directional cell locomotion requires symmetry breaking between the front and rear of the cell. In some cells, symmetry breaking manifests itself in a directional flow of actin from the front to the rear of the cell. Many cells, especially in physiological 3D matrices, do not show such coherent actin dynamics and present seemingly competing protrusion/retraction dynamics at their front and back.

Probing Intravascular Adhesion and Extravasation of Tumor Cells with Microfluidics.

Cancer metastasis is a multistep process during which tumor cells leave the primary tumor mass and form distant secondary colonies that are lethal. Circulating tumor cells (CTCs) are transported by body fluids to reach distant organs, where they will extravasate and either remain dormant or form new tumor foci. Development of methods to study the behavior of CTCs at the late stages of the intravascular journey is thus required to dissect the molecular mechanisms at play.

Mechanical Adaptability of Tumor Cells in Metastasis.

The most dangerous aspect of cancer lies in metastatic progression. Tumor cells will successfully form life-threatening metastases when they undergo sequential steps along a journey from the primary tumor to distant organs. From a biomechanics standpoint, growth, invasion, intravasation, circulation, arrest/adhesion, and extravasation of tumor cells demand particular cell-mechanical properties in order to survive and complete the metastatic cascade.

[Influence of fluid mechanics on metastasis formation].

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field.

Fluids and their mechanics in tumour transit: shaping metastasis.

Metastasis is a dynamic succession of events involving the dissemination of tumour cells to distant sites within the body, ultimately reducing the survival of patients with cancer. To colonize distant organs and, therefore, systemically disseminate within the organism, cancer cells and associated factors exploit several bodily fluid systems, which provide a natural transportation route. Indeed, the flow mechanics of the blood and lymphatic circulatory systems can be co-opted to improve the efficiency of cancer cell transit from the primary tumour, extravasation and metastatic seeding.

Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest.

Cancer metastasis is a process whereby a primary tumor spreads to distant organs. We have demonstrated previously that blood flow controls the intravascular arrest of circulating tumor cells (CTCs) through stable adhesion to endothelial cells. We now aim to define the contribution of cell adhesion potential and identify adhesion receptors at play.

-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction.

A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC ranging from 10 to 80 nM.

Wrapped stellate silica nanocomposites as biocompatible luminescent nanoplatforms assessed in vivo.

The engineering of luminescent nanoplatforms for biomedical applications displaying ability for scaling-up, good colloidal stability in aqueous solutions, biocompatibility, and providing an easy detection in vivo by fluorescence methods while offering high potential of functionalities, is currently a challenge. The original strategy proposed here involves the use of large pore (ca. 15 nm) mesoporous silica (MS) nanoparticles (NPs) having a stellate morphology (denoted STMS) on which fluorescent InP/ZnS quantum dots (QDs) are covalently grafted with a high yield (≥90%).

Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo.

Tumor extracellular vesicles (EVs) mediate the communication between tumor and stromal cells mostly to the benefit of tumor progression. Notably, tumor EVs travel in the bloodstream, reach distant organs, and locally modify the microenvironment. However, visualizing these events in vivo still faces major hurdles.

Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells.

Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium.

Using the Zebrafish Embryo to Dissect the Early Steps of the Metastasis Cascade.

Most cancers end up with the death of patients caused by the formation of secondary tumors, called metastases. However, how these secondary tumors appear and develop is only poorly understood. A fine understanding of the multiple steps of the metastasis cascade requires in vivo models allowing high spatiotemporal analysis of the behavior of metastatic cells.

Design of Protein-Coated Carbon Nanotubes Loaded with Hydrophobic Drugs through Sacrificial Templating of Mesoporous Silica Shells.

One key challenge in the fields of nanomedicine and tissue engineering is the design of theranostic nanoplatforms able to monitor their therapeutic effect by imaging. Among current developed nano-objects, carbon nanotubes (CNTs) were found suitable to combine imaging, photothermal therapy, and to be loaded with hydrophobic drugs. However, a main problem is their resulting low hydrophilicity.

Hemodynamic forces can be accurately measured in vivo with optical tweezers.

Force sensing and generation at the tissue and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo. Optical trapping allows noninvasive probing of piconewton forces and thus emerged as a promising mean for assessing biomechanics in vivo.

Seeing is believing - multi-scale spatio-temporal imaging towards in vivo cell biology.

Life is driven by a set of biological events that are naturally dynamic and tightly orchestrated from the single molecule to entire organisms. Although biochemistry and molecular biology have been essential in deciphering signaling at a cellular and organismal level, biological imaging has been instrumental for unraveling life processes across multiple scales. Imaging methods have considerably improved over the past decades and now allow to grasp the inner workings of proteins, organelles, cells, organs and whole organisms.

Metastasis of circulating tumor cells: favorable soil or suitable biomechanics, or both?

Metastasis is the end product of a multistep process where cancer cells disseminate and home themselves in distant organs. Tumor cell extravasation is a rare, inefficient and transient event in nature and makes its studies very difficult. Noteworthy, little is known about how cancer cells arrest, adhere and pass through the endothelium of capillaries.

Pulse propagation by a capacitive mechanism drives embryonic blood flow.

Pulsatile flow is a universal feature of the blood circulatory system in vertebrates and can lead to diseases when abnormal. In the embryo, blood flow forces stimulate vessel remodeling and stem cell proliferation. At these early stages, when vessels lack muscle cells, the heart is valveless and the Reynolds number (Re) is low, few details are available regarding the mechanisms controlling pulses propagation in the developing vascular network.

Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis.

Background: Hydrodynamic forces play a central role in organ morphogenesis. The role of blood flow in shaping the developing heart is well established, but the role of fluid forces generated in the pericardial cavity surrounding the heart is unknown. Mesothelial cells lining the pericardium generate the proepicardium (PE), the precursor cell population of the epicardium, the outer layer covering the myocardium, which is essential for its maturation and the formation of the heart valves and coronary vasculature.