Brain distribution study of [C]-Riluzole following intranasal administration in mice.

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.

Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.

Glioblastoma (GBM) immunotherapy is particularly challenging due to the pro-tumorigenic microenvironment, marked by low levels and inactive immune cells. Toll-like receptor (TLR) agonists have emerged as potent immune adjuvants but failed to show improved outcomes in clinical trials when administered as a monotherapy. We hypothesize that a combined nanoparticulate formulation of TLR agonist and immunogenic cell death-inducing drug (doxorubicin) will synergize to induce improved GBM immunotherapy.

RNA lipid nanoparticles as efficient in vivo CRISPR-Cas9 gene editing tool for therapeutic target validation in glioblastoma cancer stem cells.

In vitro and ex-vivo target identification strategies often fail to predict in vivo efficacy, particularly for glioblastoma (GBM), a highly heterogenous tumor rich in resistant cancer stem cells (GSCs). An in vivo screening tool can improve prediction of therapeutic efficacy by considering the complex tumor microenvironment and the dynamic plasticity of GSCs driving therapy resistance and recurrence. This study proposes lipid nanoparticles (LNPs) as an efficient in vivo CRISPR-Cas9 gene editing tool for target validation in mesenchymal GSCs.

Graphene Oxide Nanosheets Toxicity in Mice Is Dependent on Protein Corona Composition and Host Immunity.

Two-dimension graphene oxide (GO) nanosheets with high and low serum protein binding profiles (high/low hard-bound protein corona/HC) are used in this study as model materials and screening tools to investigate the underlying roles of the protein corona on nanomaterial toxicities . We proposed that the biocompatibility/nanotoxicity of GO is protein corona-dependent and host immunity-dependent. The hypothesis was tested by injecting HC GO nanosheets in immunocompetent ICR/CD1 and immunodeficient NOD- mice and performed histopathological and hematological evaluation studies on days 1 and 14 post-injection.

Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent.

Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface.

Combined Facile Synthesis, Purification, and Surface Functionalization Approach Yields Monodispersed Gold Nanorods for Drug Delivery Applications.

Synthesizing gold nanorods (AuNRs) by seed-mediated growth method results in the presence of undesired size and shape particles by-products occupying 10-90% of the population. In this study, AuNRs are synthesized by the seed-mediated growth method using cetyltrimethylammonium bromide (CTAB) as a surfactant. AuNRs with redshifted longitudinal localized surface plasmon resonance (LLSPR) peak, localized in the biological "transparency window" (650-1350 nm), are synthesized after optimizing seed solution, silver nitrate solution, and hydrochloric acid solution volumes, based on the published protocols.

Serum-derived extracellular vesicles from breast cancer patients contribute to differential regulation of T-cell-mediated immune-escape mechanisms in breast cancer subtypes.

Background: Intracellular communication within the tumour is complex and extracellular vesicles (EVs) have been identified as major contributing factors for the cell-to-cell communication in the local and distant tumour environments. Here, we examine the differential effects of breast cancer (BC) subtype-specific patient serum and cell-line derived EVs in the regulation of T cell mediated immune responses.

Methods: Ultracentrifugation was used to isolate EVs from sera of 63 BC patients, 15 healthy volunteers and 4 human breast cancer cell lines.

The interplay of solvent-drug-protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells.

Objectives: Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability.

Evaluation of a DoE based approach for comprehensive modelling of the effect of lipid nanoparticle composition on nucleic acid delivery.

Therapeutic nucleic acids (TNAs) comprise an alternative to conventional drugs for cancer therapy. Recently, stable nucleic acid lipid particles (SNALPs) have been explored to deliver TNA efficiently and safely both in vitro and in vivo. Small interfering RNA (siRNA) and messenger RNA (mRNA) based drugs have been suggested for a wide range of pathologies, and their respective lipid nanoparticle (LNP) formulations have been optimised using a Design of Experiments (DoE) approach.

Spatiotemporal tracking of gold nanorods after intranasal administration for brain targeting.

Intranasal administration is becoming increasingly more attractive as a fast delivery route to the brain for therapeutics circumventing the blood-brain barrier (BBB). Gold nanorods (AuNRs) demonstrate unique optical and biological properties compared to other gold nanostructures due to their high aspect ratio. In this study, we investigated for the first time the brain region-specific distribution of AuNRs and their potential as a drug delivery platform for central nervous system (CNS) therapy following intranasal administration to mice using a battery of analytical and imaging techniques.

Plasmid DNA cationic non-viral vector complexes induce cytotoxicity-associated PD-L1 expression up-regulation in cancer cells in vitro.

Non-viral vectors are promising nucleic acid carriers which have been utilized in gene-based cancer immunotherapy. The aim of this study is to compare the transfection efficiency and cytotoxicity of three cationic non-viral vectors namely Polyethylenimine (PEI), Lipofectamine 2000 (LPF) and stable nucleic acid lipid particles (SNALPs) of different lipid compositions, for the delivery of plasmid DNA (pDNA) expressing immunostimulatory molecules, OX40L or 4-1BBL, to cancer cells in vitro. The results indicate that PEI and LPF are efficient vectors for pDNA delivery with high transfection efficiency obtained.

Anti-tumor antibody isotype response can be modified with locally administered immunoadjuvants.

In situ vaccination with immunostimulatory compounds is a demonstrated means to treat tumors preclinically. While these therapeutic effects have been attributed to the actions of T cells or innate immune activation, characterisation of the humoral immune response is seldom performed. This study aims to identify whether the injection of immunoadjuvants, Addavax (Adda) and cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG), intratumorally can influence the antibody response.

Hyaluronic acid-entecavir conjugates-core/lipid-shell nanohybrids for efficient macrophage uptake and hepatotropic prospects.

Drug covalently bound to polymers had formed, lately, platforms with great promise in drug delivery. These drug polymer conjugates (DPC) boosted drug loading and controlled medicine release with targeting ability. Herein, the ability of entecavir (E) conjugated to hyaluronic acid (HA) forming the core of vitamin E coated lipid nanohybrids (EE-HA LPH), to target Kupffer cells and hepatocyte had been proved.

Pre-clinical non-viral vectors exploited for CRISPR/Cas9 gene editing: an overview.

Clustered regulatory interspaced short palindromic repeats or CRISPR/Cas9 has emerged as a potent and versatile tool for efficient genome editing. This technology has been exploited for several applications including disease modelling, cell therapy, diagnosis, and treatment of many diseases including cancer. The application of CRISPR/Cas9 is hindered by poor stability, pharmacokinetic profile, and the limited ability of the CRISPR payloads to cross biological barriers.

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia.

Detection of Cancer-Derived Exosomes Using a Sensitive Colorimetric Aptasensor.

Exosomes are a type of extracellular vesicles that contain constituents including proteins, DNAs, and RNAs of the cells that secrete them. Cancerous exosomes are potential biomarkers for cancer diagnosis. Biosensors are useful analytical tools for quantification of biomarkers and targeted molecules.

PET Imaging of Small Extracellular Vesicles [Zr]Zr(oxinate) Direct Radiolabeling.

Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand their biodistribution using imaging techniques that allow tracking over time and at the whole-body level. Positron emission tomography (PET) allows short- and long-term whole-body tracking of radiolabeled compounds in both animals and humans and with excellent quantification properties compared to other nuclear imaging techniques.

Functionalization of filled radioactive multi-walled carbon nanocapsules by arylation reaction for delivery of radio-therapy.

Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (SmCl), the ends of the MWCNTs are sealed by high temperature treatment, and the encapsulated Sm is neutron activated to radioactive Sm. The external walls of the radioactive nanocapsules are functionalized through arylation reaction, to introduce hydrophilic chains and increase the water dispersibility of CNTs.

Bioengineering of virus-like particles as dynamic nanocarriers for in vivo delivery and targeting to solid tumours.

Virus-like particles (VLPs) are known as self-assembled, non-replicative and non-infectious protein particles, which imitate the formation and structure of original wild type viruses, however, lack the viral genome and/or their fragments. The capacity of VLPs to encompass small molecules like nucleic acids and others has made them as novel vessels of nanocarriers for drug delivery applications. In addition, VLPs surface have the capacity to achieve variation of the surface display via several modification strategies including genetic modification, chemical modification, and non-covalent modification.

Modulating expression of inhibitory and stimulatory immune 'checkpoints' using nanoparticulate-assisted nucleic acid delivery.

Immune checkpoints are regulatory molecules responsible for determining the magnitude and nature of the immune response. The aim of immune checkpoint targeting immunotherapy is to manipulate these interactions, engaging the immune system in treatment of cancer. Clinically, the use of monoclonal antibodies to block immunosuppressive interactions has proven itself to be a highly effective immunotherapeutic intervention.

A natural protein based platform for the delivery of Temozolomide acid to glioma cells.

Glioblastoma is one of the most difficult to treat cancers with poor prognosis and survival of around one year from diagnosis. Effective treatments are desperately needed. This work aims to prepare temozolomide acid (TMZA) loaded albumin nanoparticles, for the first time, to target glioblastoma (GL261) and brain cancer stem cells (BL6).

Nanoparticle-Mediated Molecular Reprogramming of Immune Checkpoint Interactions for Cancer Immunotherapy.

Immune checkpoint blockade involves targeting immune regulatory molecules with antibodies. Preclinically, complex multiantibody regimes of both inhibitory and stimulatory targets are a promising candidate for the next generation of immunotherapy. However, in this setting, the antibody platform may be limited due to excessive toxicity caused by off target effects as a result of systemic administration.

Recent progress in nanotechnology-based drug carriers for celastrol delivery.

Celastrol (CLT) is an active ingredient that was initially discovered and extracted from the root of The potential pharmacological activities of CLT in cancer, obesity, and inflammatory, auto-immune, and neurodegenerative diseases have been demonstrated in recent years. However, CLT's clinical application is extremely restricted by its low solubility/permeability, poor bioavailability, and potential off-target toxicity. The advent of nanotechnology provides a solution to improve the oral bioavailability, therapeutic effects or tissue-targeting ability of CLT.