Particle therapy

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective...

Cherenkov imaging is an ideal tool for real-time in vivo verification of a radiation therapy dose. Given that radiation is pulsed from a medical linear accelerator (LINAC) together with weak Cherenkov emissions, time-gated high-sensitivity imaging is required for robust measurements. Instead of using an expensive camera system with limited efficiency of detection in each pixel, a single-pixel imaging (SPI) approach that maintains promising sensitivity over the entire spectral band could be used to provide a low-cost and viable alternative...

There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell...

SIGNIFICANCE: Assessing the nanostructure of polymer solutions and biofluids is broadly useful for understanding drug delivery and disease progression and for monitoring therapy. AIM: Our objective is to quantify bronchial mucus solids concentration (wt. %) during hypertonic saline (HTS) treatment in vitro via nanostructurally constrained diffusion of gold nanorods (GNRs) monitored by polarization-sensitive optical coherence tomography (PS-OCT). APPROACH: Using PS-OCT, we quantified GNR translational (<mml:math xmlns:mml="https://www...

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body...

Targeted radionuclide therapy (TRT) has significantly evolved from its beginnings with iodine-131 to employing carrier molecules with beta emitting isotopes like lutetium-177. With the success of Lu-177-DOTATATE for neuroendocrine tumors and Lu-177-PSMA-617 for prostate cancer, several other beta emitting radioisotopes, such as Cu-67 and Tb-161, are being explored for TRT. The field has also expanded into targeted alpha therapy (TAT) with agents like radium-223 for bone metastases in prostate cancer, and several other alpha emitter radioisotopes with carrier molecules, such as Ac-225, and Pb-212 under clinical trials...

Over 50 million people worldwide are affected by epilepsy, a common neurological disorder that has a high rate of drug resistance and diverse comorbidities such as progressive cognitive and behavioural disorders, and increased mortality from direct or indirect effects of seizures and therapies. Despite extensive research with animal models and human studies, limited insights have been gained into the mechanisms underlying seizures and epileptogenesis, which has not translated into significant reductions in drug resistance, morbidities, or mortality...

Biomolecule-functionalized nanoparticles represent a type of promising biomaterials in biomedical applications owing to their excellent biocompatibility and versatility. DNA-based reactions on nanoparticles have enabled emerging applications including intelligent biosensors, drug delivery, and biomimetic devices. Among the reactions, strand hybridization is the critical step to control the sensitivity and specificity of biosensing, and the efficiency of drug delivery. However, a comprehensive understanding of DNA hybridization on nanoparticles is still lacking, which may differ from the process in homogeneous solutions...

BACKGROUND: Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC). Nanogels (NGs) offer a novel oral drug delivery system, ideal for hydrophilic compounds like GEM. This study aims to develop NGs tailored for GEM delivery, with the goal of enhancing cellular uptake and gastrointestinal permeability for improved administration in PDAC patients...

Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8+ T cells to achieve a therapeutic response in vivo. This was done by delivering single or multiple microRNAs to primary naïve mouse and human CD8+ T cells without pre-activation...

Allogeneic cell therapies, such as those involving macrophages or Natural Killer (NK) cells, are of increasing interest for cancer immunotherapy. However, the current techniques for genetically modifying these cell types using lenti- or gamma-retroviral vectors present challenges, such as required cell pre-activation and inefficiency in transduction, which hinder the assessment of preclinical efficacy and clinical translation. In our study, we describe a novel lentiviral pseudotype based on the Koala Retrovirus (KoRV) envelope protein, which we identified based on homology to existing pseudotypes used in cell therapy...

While adeno-associated virus is a leading vector for gene therapy, significant gaps remain in understanding AAV degradation and stability. In this work, we study the degradation of an engineered AAV serotype at physiological pH and ionic strength. Viral particles of varying fractions of encapsulated DNA were incubated between 30 and 60 °C, with changes in molecular weight measured by changes in total light scattering intensity at 90° over time. Mostly full vectors demonstrated a rapid decrease in molecular weight corresponding to the release of capsid DNA, followed by slow aggregation...

Previously, we reported a neutralizing monoclonal antibody, A8A11, raised against a novel conserved epitope within the hepatitis C virus (HCV) E2 protein, that could significantly reduce HCV replication. Here, we report the nucleotide sequence of A8A11 and demonstrate the efficacy of a single-chain variable fragment (scFv) protein that mimics the antibody, inhibits the binding of an HCV virus-like particle to hepatocytes, and reduces viral RNA replication in a cell culture system. More importantly, scFv A8A11 was found to effectively restrict the increase of viral RNA levels in the serum of HCV-infected chimeric mice harbouring human hepatocytes...

Natural polyphenolic compounds play a vital role in nature and are widely utilized as building blocks in the fabrication of emerging functional nanomaterials. Although diverse fabrication methodologies are developed in recent years, the challenges of purification, uncontrollable reaction processes and additional additives persist. Herein, a modular and facile methodology is reported toward the fabrication of natural polyphenolic nanoparticles. By utilizing low frequency ultrasound (40 kHz), the assembly of various natural polyphenolic building blocks is successfully induced, allowing for precise control over the particle formation process...

Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy...

Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions...

The development of nanoparticle (NP)-based drug carriers has presented an exciting opportunity to address challenges in oncology. Among the 100,000 available possibilities, zirconium-based metal-organic frameworks (MOFs) have emerged as promising candidates in biomedical applications. Zr-MOFs can be easily synthesized as small-size NPs compatible with intravenous injection, whereas the ease of decorating their external surfaces with functional groups allows for targeted treatment. Despite these benefits, Zr-MOFs suffer degradation and aggregation in real, in vivo conditions, whereas the loaded drugs will suffer the burst effect-i...

Oral targeted anti-inflammatory drugs have garnered significant interest in treating ulcerative colitis (UC) due to their potential in reducing medical costs and enhancing treatment efficacy. Magnolol (Mag), a natural anti-inflammatory compound, has demonstrated protective effects against UC. However, its application as an alternative therapeutic agent for UC is limited by poor gastrointestinal stability and inadequate accumulation at inflamed colonic lesions. This study introduces a novel nanoparticle (NPs) formulation based on Mag, functionalized with hyaluronic acid (HA) for targeted UC therapy...

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated...

Toxocara is a genus of nematodes, which infects a variety of hosts, principally dogs and cats, with potential zoonotic risks to humans. Toxocara spp. larvae are capable of migrating throughout the host tissues, eliciting eosinophilic and granulomatous reactions, while surviving for extended periods of time, unchanged, in the host. It is postulated that larvae are capable of altering the host's immune response through the release of excretory-secretory products, containing both proteins and extracellular vesicles (EVs)...