Acid-Sphingomyelinase Triggered Fluorescently Labeled Sphingomyelin Containing Liposomes in Tumor Diagnosis after Radiation-Induced Stress

In liposomal delivery, a big question is how to release the loaded material into the correct place. Here, we will test the targeting and release abilities of our sphingomyelin-consisting liposome. A change in release parameters can be observed when sphingomyelin-containing liposome is treated with sphingomyelinase enzyme. Sphingomyelinase is known to be endogenously released from the different cells in stress situations. We assume the effective enzyme treatment will weaken the liposome making it also leakier. To test the release abilities of the SM-liposome, we developed several fluorescence-based experiments. In in vitro studies, we used molecular quenching to study the sphingomyelinase enzyme-based release from the liposomes. We could show that the enzyme treatment releases loaded fluorescent markers from sphingomyelin-containing liposomes. Moreover, the release correlated with used enzymatic activities. We studied whether the stress-related enzyme expression is increased if the cells are treated with radiation as a stress inducer. It appeared that the radiation caused increased enzymatic activity. We studied our liposomes' biodistribution in the animal tumor model when the tumor was under radiation stress. Increased targeting of the fluorescent marker loaded to our liposomes could be found on the site of cancer. The liposomal targeting in vivo could be improved by radiation. Based on our studies, we propose sphingomyelin-containing liposomes can be used as a controlled release system sensitive to cell stress

Imaging Inflammation - From Whole Body Imaging to Cellular Resolution

Imaging techniques have evolved impressively lately, allowing whole new concepts like multimodal imaging, personal medicine, theranostic therapies, and molecular imaging to increase general awareness of possiblities of imaging to medicine field. Here, we have collected the selected (3D) imaging modalities and evaluated the recent findings on preclinical and clinical inflammation imaging. The focus has been on the feasibility of imaging to aid in inflammation precision medicine, and the key challenges and opportunities of the imaging modalities are presented. Some examples of the current usage in clinics/close to clinics have been brought out as an example. This review evaluates the future prospects of the imaging technologies for clinical applications in precision medicine from the pre-clinical development point of view

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release

Simple Summary A novel active release system magnetic sphingomyelin-containing liposome encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin was evaluated. The liposomal sphingomyelin is a target for the sphingomyelinase enzyme, which is released by stressed cells. Thus, sphingomyelin containing liposomes behave as a sensitizer for biological stress situations. In addition, the liposomes were engineered by adding paramagnetic beads to act as a receiver of outside given magnetic energy. The enzymatic activity towards liposomes and destruction caused by the applied magnetic field caused the release of the content from the liposomes. By using these novel liposomes, we could improve the drug release feature of liposomes. The improved targeting and drug-release were shown in vitro and the orthotopic tongue cancer model in mice optical imaging. The increased delivery of cisplatin prolonged the survival of the targeted delivery group versus free cisplatin. Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.Peer reviewe

Exploring the Usability of α-MSH-SM-Liposome as an Imaging Agent to Study Biodegradable Bone Implants In Vivo

Novel biodegradable metal alloys are increasingly used as implant materials. The implantation can be accompanied by an inflammatory response to a foreign object. For studying inflammation in the implantation area, non-invasive imaging methods are needed. In vivo imaging for the implanted area and its surroundings will provide beneficiary information to understand implant-related inflammation and help to monitor it. Therefore, inflammation-sensitive fluorescent liposomes in rats were tested in the presence of an implant to evaluate their usability in studying inflammation. The sphingomyelin-containing liposomes carrying alpha-melanocyte-stimulating hormone (α-MSH)-peptide were tested in a rat bone implant model. The liposome interaction with implant material (Mg-10Gd) was analyzed with Mg-based implant material (Mg-10Gd) in vitro. The liposome uptake process was studied in the bone-marrow-derived macrophages in vitro. Finally, this liposomal tracer was tested in vivo. It was found that α-MSH coupled sphingomyelin-containing liposomes and the Mg-10Gd implant did not have any disturbing influence on each other. The clearance of liposomes was observed in the presence of an inert and biodegradable implant. The degradable Mg-10Gd was used as an alloy example; however, the presented imaging system offers a new possible use of α-MSH-SM-liposomes as tools for investigating implant responses