- Ultrasound and Hyperthermia Applications
- Nanoparticle-Based Drug Delivery
- Photoacoustic and Ultrasonic Imaging
- Ultrasound and Cavitation Phenomena
- Nanoplatforms for cancer theranostics
- Inhalation and Respiratory Drug Delivery
- Immune cells in cancer
- Gold and Silver Nanoparticles Synthesis and Applications
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Advanced Drug Delivery Systems
- Radiation Therapy and Dosimetry
- Cancer Research and Treatment
- Ultrasound Imaging and Elastography
- Nanoparticles: synthesis and applications
- Advanced Breast Cancer Therapies
- Intraperitoneal and Appendiceal Malignancies
- Cerebrospinal fluid and hydrocephalus
- Peptidase Inhibition and Analysis
- Electrohydrodynamics and Fluid Dynamics
- MRI in cancer diagnosis
- Phosphodiesterase function and regulation
- Blood transfusion and management
- Graphene and Nanomaterials Applications
- Glioma Diagnosis and Treatment
Norwegian University of Science and Technology
2015-2024
St Olav's University Hospital
2018-2024
SINTEF
2018-2024
Cancer Clinic
2021
Abstract In vitro and in vivo behavior of nanoparticles (NPs) is often studied by tracing the NPs with fluorescent dyes. This requires stable incorporation dyes within NPs, as dye leakage may give a wrong interpretation NP biodistribution, cellular uptake, intracellular distribution. Furthermore, labeling trace amounts should not alter properties such interactions cells or tissues. To allow for versatile studies variety fluorescence‐based assays, different desirable. Hence, when new are...
Compared with conventional chemotherapy, encapsulation of drugs in nanoparticles can improve efficacy and reduce toxicity. However, delivery is often insufficient heterogeneous because various biological barriers uneven tumor perfusion. We investigated a unique multifunctional drug system consisting microbubbles stabilized by polymeric (NPMBs), enabling ultrasound-mediated delivery. The aim was to examine mechanisms determine if increased uptake had therapeutic benefit. Cellular toxicity,...
Microbubbles (MBs) are routinely used as contrast agents for ultrasound imaging. The use of in combination with MBs has also attracted attention a method to enhance drug delivery. We have developed technology platform incorporating multiple functionalities, including imaging and therapy single system consisting stabilized by polyethylene glycol (PEG)‐coated polymeric nanoparticles (NPs). NPs, containing lipophilic drugs and/or agents, composed the widely poly(butyl cyanoacrylate) (PBCA)...
The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering brain. Focused ultrasound (FUS) with microbubbles can open BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized to permeabilize melanoma metastasis model. With dual-frequency transducer...
Encapsulation of drugs in nanoparticles can enhance the accumulation tumours, reduce toxicity toward healthy tissue, and improve pharmacokinetics compared to administration free drug. To achieve efficient delivery release at target site, mechanisms interaction between cells mechanism encapsulated drug are crucial understand. Our aim was determine for cellular uptake a fluorescent hydrophobic model from poly(butylcyanoacrylate) nanoparticles. Prostate adenocarcinoma were incubated with Nile...
The effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown mammary fat pad immunodeficient mice. Nanoparticle-encapsulated had a much better efficacy than similar concentrations free resulted complete remission 6 out 8 tumors, whereas gave only with 2 9 tumors. To investigate different efficacies obtained nanoparticle-encapsulated versus...
To improve therapeutic efficacy of nanocarrier drug delivery systems, it is essential to their uptake and penetration in tumour tissue, enhance cellular ensure efficient release at the site. Here we introduce a targeting system based on ultrasound-mediated enzyme sensitive liposomes. These liposomes are coated with cleavable poly(ethylene glycol) (PEG) which will be cleaved by two members matrix metalloproteinase family (MMP-2 MMP-9). Cleavage PEG coat can increase destabilize liposomal...
Delivery of drugs and nanomedicines to tumors is often heterogeneous insufficient and, thus, limited efficacy. Microbubbles in combination with ultrasound have been found improve delivery tumors, enhancing accumulation penetration. We used a subcutaneous prostate cancer xenograft model mice investigate the effect free nanoparticle-encapsulated cabazitaxel microbubbles lipid shell or nanoparticles. Sonopermeation reduced tumor growth prolonged survival (26%-100%), whether drug was co-injected...
The aim of this study was to develop high load-capacity antibubbles that can be visualized using diagnostic ultrasound and the encapsulated drug released delivered clinically translatable ultrasound. were developed by optimising a silica nanoparticle stabilised double emulsion template. We produced an with mean size diameter 4.23 ± 1.63 µm where 38.9 3.1% droplets contained one or more cores. Following conversion antibubbles, decreased 2.96 1.94 99% <10 µm. had peak attenuation 4.8 dB/cm at...
Abstract Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shape, chemical composition and surface properties encapsulating nanoparticle, and, thus, less dependent on physicochemical active pharmaceutical ingredient encapsulated. In current work, we aimed to investigate impact formulation type biodistribution profile for two clinically relevant nanoformulations. We performed a comparative study in healthy rats at several dose levels durations up...
Colorectal and ovarian cancers frequently develop peritoneal metastases with few treatment options. Intraperitoneal chemotherapy has shown promising therapeutic effects, but is limited by rapid drug clearance systemic toxicity. We therefore encapsulated the cabazitaxel taxane in poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs), designed to improve intraperitoneal delivery. Toxicity of free was investigated rats monitoring clinical signs, organ weight blood hematological biochemical...
Treatment of glioblastoma and other diseases in the brain is especially challenging due to blood-brain barrier, which effectively protects parenchyma.In this study we show for first time that cabazitaxel, a semi-synthetic derivative docetaxel can cross barrier give significant therapeutic effect patient-derived orthotopic model glioblastoma.We drug crosses more tumor than healthy reduced expression p-glycoprotein efflux pumps vasculature tumor.Surprisingly, neither ultrasound-mediated...
Ultrasound and microbubbles have been found to improve the delivery of drugs nanoparticles tumor tissue. To obtain new knowledge on influence vascular parameters extravasation elucidate effect acoustic pressure penetration nanoscale particles into extracellular matrix, real-time intravital multiphoton microscopy was performed during sonication tumors growing in dorsal window chambers. The impact vessel diameter, structure blood flow characterized. Fluorescein isothiocyanate–dextran (2 MDa)...
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there no standardized route to surpass it. One technique locally transiently disrupt BBB, focused ultrasound combination with gas-filled microbubbles. However, microbubbles used are typically developed imaging, not BBB disruption. Here we describe efficient opening using promising novel Acoustic Cluster Therapy (ACT), that recently has been Abraxane® successfully treat subcutaneous tumors...
Therapeutic agents can benefit from encapsulation in nanoparticles, due to improved pharmacokinetics and biodistribution, protection degradation, increased cellular uptake sustained release. Microbubbles combination with ultrasound have been shown improve the delivery of nanoparticles drugs tumors across blood-brain barrier. Here, we evaluate two different microbubbles for enhancing polymeric cells vitro: a commercially available lipid microbubble (Sonazoid) shell composed protein...
ObjectiveCurrently available cytotoxic treatments have limited effect on pancreatic ductal adenocarcinoma (PDAC) because desmoplastic stroma limits drug delivery. Efforts been made to overcome these barriers by targeting the tumor microenvironment. Results so far are promising, but without clinical impact. Our aim was investigate whether ultrasound and microbubbles could improve uptake therapeutic response of conventional chemotherapy.MethodsOrthotopic tumors growing in mice were treated...
Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor based on four cell lines were characterized, including metastatic lung cancer (CMT 167), triple-negative breast (4T1), pancreatic (KPCY), and colon (MC38). The tumors implanted subcutaneously or orthotopically before the animals treated with anti-PD1 checkpoint inhibitor. A range innate adaptive immune cells then quantified by flow cytometry single-cell...
Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance chemotherapy and complex tumour microenvironment characterised by stromal desmoplasia. There is need for new strategies improve the delivery of drugs therapeutic response. Relevant preclinical models are needed test potential treatments. This paper compared orthotopic subcutaneous PDAC their suitability drug studies. A novel aspect was broad range properties that were studied, including...
Protein adsorption on nanoparticles (NPs) used in nanomedicine leads to opsonization and activation of the complement system blood, which substantially reduces blood circulation time NPs. The most commonly method avoid protein is coat NPs with polyethylene glycol, so-called PEGylation. Although PEGylation utmost importance for designing vivo behavior NP, there still a considerable lack methods characterization fundamental understanding related In this work we have studied four different...
Abstract Drug delivery to tumors is challenging due biological barriers obstructing effective delivery. Sonopermeation with ultrasound and microbubbles has been shown improve therapeutic effect of many classes drugs, but the underlying mechanism not fully understood. In this study, two subcutaneous xenograft tumor models, that differed substantially in blood vessel density stiffness, treated poly(alkyl cyanoacrylate) nanoparticles nanoparticle‐stabilized combined ultrasound. Improved...