Imaging Delivery Research Articles

Application of nanoliposome as contrast agents for magnetic resonance imaging technique

AbstractLiposomes, nano‐sized vesicles primarily comprising phospholipids and cholesterol, have emerged as pivotal tools in medical imaging, notably in magnetic resonance imaging (MRI), due to their biocompatibility and ability to encapsulate diverse molecules. Tailorable properties like size, surface charge, and encapsulation capacity make liposomes ideal for targeted delivery of imaging agents and drugs to specific tissues, improving pharmacokinetics. As MRI contrast agent (CA) carriers, liposomes encapsulate gadolinium, mitigating toxicity and boosting relaxivity and circulation times. Functionalization with targeting ligands and stimuli‐responsive designs enhances their controlled release and targeted delivery capabilities, crucial for cancer imaging and therapy. Benefits include reduced toxicity, prolonged circulation, targeted delivery, enhanced bioavailability, and potential for multimodal imaging. Challenges remain, such as stability, clearance, and manufacturing intricacies, requiring further research. Nonetheless, liposomal MRI CAs hold promise for enhancing diagnostic precision and therapeutic effectiveness in oncology and neurology, offering a robust pathway for future biomedical advancements. Addressing existing limitations could unlock their full potential in improving patient care and outcomes.

Intranasal delivery of imaging agents to the brain.

The potential of intranasal administered imaging agents to altogether bypass the blood-brain barrier offers a promising non-invasive approach for delivery directly to the brain. This review provides a comprehensive analysis of the advancements and challenges of delivering neuroimaging agents to the brain by way of the intranasal route, focusing on the various imaging modalities and their applications in central nervous system diagnostics and therapeutics. The various imaging modalities provide distinct insights into the pharmacokinetics, biodistribution, and specific interactions of imaging agents within the brain, facilitated by the use of tailored tracers and contrast agents. Methods: A comprehensive literature search spanned PubMed, Scopus, Embase, and Web of Science, covering publications from 1989 to 2024 inclusive. Starting with advancements in tracer development, we going to explore the rationale for integration of imaging techniques, and the critical role novel formulations such as nanoparticles, nano- and micro-emulsions in enhancing imaging agent delivery and visualisation. Results: The review highlights the use of innovative formulations in improving intranasal administration of neuroimaging agents, showcasing their ability to navigate the complex anatomical and physiological barriers of the nose-to-brain pathway. Various imaging techniques, MRI, PET, SPECT, CT, FUS and OI, were evaluated for their effectiveness in tracking these agents. The findings indicate significant improvements in brain targeting efficiency, rapid uptake, and sustained brain presence using innovative formulations. Conclusion: Future directions involve the development of optimised tracers tailored for intranasal administration, the potential of multimodal imaging approaches, and the implications of these advancements for diagnosing and treating neurological disorders.

Tailoring PEGylated nanoparticle surface modulates inflammatory response in vascular endothelial cells

Polymer nanoparticles (NPs) are extensively studied as drug delivery systems for various therapeutic indications, including drug and imaging agent delivery to the brain. Despite intensive research, their toxicological profile has yet to be fully characterized. In particular, the more subtle effects of nanomaterials on inflammatory processes have scarcely been investigated. Surface properties of NPs are amongst parameters governing interactions between living cells and NPs. They could considerably influence the toxicity and inflammatory response of the cells exposed to NPs.Polymeric NPs investigated here present a core-shell structure. The core is constituted of hydrophobic poly(lactic acid) (PLA) block and the surface is composed of a shell of hydrophilic block of polyethylene glycol (PEG). The effect of PEG chain length coating on the expression of genes involved in the inflammation response was investigated in two vascular endothelial cell lines (bEnd.3 and HUVEC) by qPCR. Moreover, ROS generation following NP uptake was evaluated.PEGylated NPs induce a mild and transient activation of inflammatory cytokine and chemokine genes. However, differences in PEG chain length did not show any significant effect on cytokine and chemokine gene expression and PEGylated NPs did not trigger ROS generation.The present results could contribute significantly to a deeper understanding of nanomaterial interactions and toxicity with vascular endothelial cells, guiding scientists in material coating choices.

Identification of a novel colon adenocarcinoma cell targeting peptide using phage display library biopanning.

Phage display is well recognized as a promising high-throughput screening tool for the discovery of novel cancer-targeting peptides. Here, we screened a phage display library of 7-mer random peptides through in vitro biopanning to isolate peptide ligands binding to SW480 human colon adenocarcinoma cells. Three rounds of negative and positive selection caused a remarkable enrichment of colon cancer cell-binding phage clones with a significant enhancement of phage recovery efficiency (about 157-fold). A number of phage clones were picked out from the eluted phages of last selection round and sequenced. According to the results of cell binding assay and phage cell-based ELISA, one of the isolated peptides denoted as CCBP1 (with the sequence HAMRAQP) was indicated to have the highest binding efficiency, selectivity, and specificity toward colon cancer cells with no significant binding to control cells. Peptide competitive inhibition assay revealed that binding of the phage-displayed CCBP1 is competitively inhibited by the same free peptide, suggesting that CCBP1 specific binding to the target cell is independent of the phage context. Taken together, our findings provide support for the notion that CCBP1 binds specifically to colon cancer cells and might be a potential lead candidate for targeted delivery of imaging agents or therapeutic genes/drugs to colon tumors.

Exosomes in atherosclerosis: Convergence on macrophages.

As the primary cells of atherosclerotic plaques, macrophages play a central role in the occurrence and progression of atherosclerosis (AS). In recent years, macrophages have received extensive attention as therapeutic targets. Exosomes, as natural nanoparticles, have high biocompatibility and strong targeting ability and have been widely studied as imaging agents and drug carriers. Studies on the relationship between atherosclerotic macrophages and exosomes have been focused on for the past few years. Nevertheless, no complex review has been undertaken in this area. In this review, we summarize in detail the role of macrophages in atherosclerosis, especially their plasticity and phenotypic and distributional heterogeneity. Based on the high correlation between macrophages and the pathological process of atherosclerosis, as well as the targeting of exosomes, we further review the clinical application of targeting macrophage-associated exosomes. We focus on the role of macrophage-associated exosomes in the phenotypic transformation of cells in atherosclerosis, providing a new idea for the clinical application of targeting macrophage-associated exosomes. Finally, we specifically summarize and prospect the diagnosis of macrophage-associated exosomes, such as imaging agent delivery, biomarkers and therapeutic strategies.

In silico identification and experimental validation of cellular uptake and intracellular labeling by a new cell penetrating peptide derived from CDN1

Bioactive therapeutic molecules are generally impermeable to the cell membrane, hindering their utility and efficacy. A group of peptides called cell-penetrating peptides (CPPs) were found to have the capability of transporting different types of cargo molecules across the cell membrane. Here, we identified a short peptide named P2, which has a higher proportion of basic residues than the CDN1 (cyclin-dependent kinase inhibitor 1) protein it is derived from, and we used bioinformatic analysis and experimental validation to confirm the penetration property of peptide P2. We found that peptide P2 can efficiently enter different cell lines in a concentration-dependent manner. The endocytosis pathway, especially receptor-related endocytosis, may be involved in the process of P2 penetration. Our data also showed that peptide P2 is safe in cultured cell lines and red blood cells. Lastly, peptide P2 can efficiently deliver self-labeling protein HaloTag into cells for imaging. Our study illustrates that peptide P2 is a promising imaging agent delivery vehicle for future applications.

Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles.

Insult to the central nervous system (CNS) results in an early inflammatory response, which can be exploited as an initial indicator of neurological dysfunction. Nanoparticle drug delivery systems provide a mechanism to increase the uptake of drugs into specific cell types in the CNS such as microglia, the resident macrophage responsible for innate immune response. In this study, we developed two nanoparticle-based carriers as potential theranostic systems for drug delivery to microglial cells. Poly(lactic-co-glycolic) acid (PLGA)- and l-tyrosine polyphosphate (LTP)-based nanoparticles were synthesized to encapsulate the magnetic resonance imaging (MRI) contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd[DTPA]), or the anti-inflammatory drug, rolipram. Robust uptake of both polymer formulations by microglial cells was observed with no evidence of toxicity. In mixed glial cultures, we observed a preferential internalization of nanoparticles by microglia compared to that of astrocytes. Moreover, exposure of our nanoparticles to microglial cells did not induce the release of the proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), or interleukin-6 (IL-6). These studies provide a foundation for the development of LTP nanoparticles as a platform for the delivery of imaging agents and drugs to the sites of neuroinflammation.

High-affinity peptide ligand LXY30 for targeting \u03b13\u03b21 integrin in non-small cell lung cancer

Backgroundα3β1 integrin is a promising cancer biomarker and drug target. We previously identified a 9-amino-acid cyclic peptide LXY30 for detecting α3β1 integrin on the surface of live tumor cells. This study was undertaken to characterize LXY30 in the detection, cellular function, imaging, and targeted delivery of in vitro and in vivo non-small cell lung cancer (NSCLC) models.MethodsThe whole-cell binding assay was performed by incubating NSCLC cells, extracellular vesicles (EVs), and peripheral blood mononuclear cells (PBMCs) with TentaGel resin beads coated with LXY30. In this study, we defined the nanosize EVs as exosomes, which were characterized by flow cytometry, transmission electron microscopy, dynamic light scattering, and Western blots. The function of LXY30 was determined by modulating the epidermal growth factor receptor (EGFR) signaling pathway by growth inhibition and Western blots. For in vivo biodistribution, mice bearing subcutaneous and intracranial NSCLC xenograft tumors were administrated intraveneously with LXY30-biotin/streptavidin-Cy5.5 complex and then analyzed for in vivo and ex vivo optical imaging and histopathology.ResultsWe showed that LXY30 specifically and sensitively detected α3β1 integrin-expressing NSCLC cells and tumor-derived exosomes. Tumor DNA isolated from LXY30-enriched plasma exosomes might be used to detect driver oncogenic mutations in patients with metastatic NSCLC. LXY30 only enriches tumor cells but not neutrophils, macrophages, or monocytes in the malignant pleural effusion of NSCLC patients for detecting genomic alterations by next-generation sequencing. LXY30 detected increased α3β1 integrin expression on the EGFR-mutant NSCLC cells with acquired resistance to erlotinib compared to parental erlotinib-sensitive EGFR-mutant NSCLC cells. We further showed that LXY30 modulated the EGFR signaling pathway independently from another peptide ligand LXW64 targeting αvβ3 integrin in erlotinib-resistant, EGFR-mutant H1975 cells. Analysis of The Cancer Genome Atlas (TCGA) revealed high α3 integrin expression was associated with poor prognosis in lung squamous cell carcinoma. LXY30-biotin/streptavidin-Cy5.5 complex had higher uptakes in the subcutaneous and intracranial xenografts of various α3β1 integrin-expressing lung adenocarcinoma and patient-derived lung squamous cell carcinoma xenografts while sparing the surrounding normal tissues.ConclusionLXY30 is a promising peptide for the cancer diagnosis and in vivo targeted delivery of imaging agents and cancer drugs in NSCLC, independent of histology and tumor genotype.

A Self‐Assembled Fluorescent Nanoprobe for Imaging and Therapy of Cardiac Ischemia/Reperfusion Injury

AbstractThere is a strong medical need for precision imaging of ischemic tissue and even more so for delivery of drugs specifically to the ischemic tissue at risk of functional damage. To date, no targeting epitopes or mechanisms have been established in ischemia/reperfusion injury that allow specific molecular targeting for either diagnosis or therapy, a deficiency that contributes to myocardial infarction being the leading cause of mortality and a major contributor to morbidity worldwide. Reactive oxygen species (ROS) are locally increased at the site of ischemia/reperfusion injury. Utilizing these as a unique molecular targeting mechanism in developing ROS‐responsive nanoparticles, this study illustrates unique designed ROS‐responsive, self‐assembled fluorescent nanoparticles as tools for diagnostic and therapeutic targeting of tissue that is undergoing ischemia/reperfusion injury. This ROS‐responsive fluorescent nanoprobe has been evaluated in a mouse model of myocardial infarction, applying 1 h of ischemia via temporary ligation of the left anterior descending coronary artery and measuring fluorescence signals after reperfusion. This study shows highly specific targeting to the ischemic/reperfused myocardium throughout the first 24 h post reperfusion. Overall, this study identifies ROS‐responsive fluorescent nanoparticles as an ideal platform for the localized delivery of imaging agents and novel therapeutics to the infarcted myocardium.

Biologically-derived nanomaterials for targeted therapeutic delivery to the brain.

Delivery of imaging agents and pharmaceutical payloads to the central nervous system (CNS) is essential for efficient diagnosis and treatment of brain diseases. However, therapeutic delivery is often restricted by the blood-brain barrier (BBB), which prevents transport of clinical compounds to their region of interest. This review discusses the methods that have been used to avoid or overcome this barrier, presenting the use of biologically-derived nanomaterial systems as an efficient strategy for the diagnosis and treatment of CNS diseases. Biological nanomaterials have many advantages over synthetic systems, including being biodegradable, biocompatible, easily surface functionalised for conjugation of targeting moieties, and are often able to self-assemble. These abilities are discussed in relation to various systems, including liposomes, dendrimers, and viral nanoparticles.

Treatment of pancreatic ductal adenocarcinoma with tumor antigen specific-targeted delivery of paclitaxel loaded PLGA nanoparticles

BackgroundPancreatic ductal adenocarcinoma (PDA) remains the most aggressive cancers with a 5-year survival below 10%. Systemic delivery of chemotherapy drugs has severe side effects in patients with PDA and does not significantly improve overall survival rate. It is highly desirable to advance the therapeutic efficacy of chemotherapeutic drugs by targeting their delivery and increasing accumulation at the tumor site. MUC1 is a membrane-tethered glycoprotein that is aberrantly overexpressed in > 80% of PDA thus making it an attractive antigenic target.MethodsPoly lactic-co-glycolic acid nanoparticles (PLGA NPs) conjugated to a tumor specific MUC1 antibody, TAB004, was used as a nanocarrier for targeted delivery into human PDA cell lines in vitro and in PDA tumors in vivo. The PLGA NPs were loaded with fluorescent imaging agents, fluorescein diacetate (FDA) and Nile Red (NR) or isocyanine green (ICG) for in vitro and in vivo imaging respectively or with a chemotherapeutic drug, paclitaxel (PTX) for in vitro cytotoxicity assays. Confocal microscopy was used to visualize internalization of the nanocarrier in vitro in PDA cells with high and low MUC1 expression. The in vivo imaging system (IVIS) was used to visualize in vivo tumor targeting of the nanocarrier. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to determine in vitro cell survival of cells treated with PTX-loaded nanocarrier. One-sided t-test comparing treatment groups at each concentration and two-way ANOVAs comparing internalization of antibody and PLGA nanoparticles.ResultsIn vitro, TAB004-conjugated ICG-nanocarriers were significantly better at internalizing in PDA cells than its non-conjugated counterpart. Similarly, TAB004-conjugated PTX-nanocarriers were significantly more cytotoxic in vitro against PDA cells than its non-conjugated counterpart. In vivo, TAB004-conjugated ICG-nanocarriers showed increased accumulation in the PDA tumor compared to the non-conjugated nanocarrier while sparing normal organs.ConclusionsThe study provides promising data for future development of a novel MUC1-targeted nanocarrier for direct delivery of imaging agents or drugs into the tumor microenvironment.

Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs.

Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively. The uptake of dye-labeled particles was tested in a range of cancer cells and monitored by confocal microscopy and flow cytometry. VLPs labeled internally on cysteine residues were taken up with high efficiency by several cancer cell lines and were colocalized with the endolysosomal marker LAMP-1 within 6 h, whereas VLPs labeled externally on lysine residues were taken up with lower efficiency, probably reflecting differences in surface charge and the propensity to bind to the cell surface. The infusion of dye and drug molecules into the cavity of the VLPs revealed that the photosensitizer (PS), Zn-EpPor, and the drugs crystal violet, mitoxantrone (MTX), and doxorubicin (DOX) associated stably with the carrier via noncovalent interactions. We confirmed the cytotoxicity of the PS-PhMV and DOX-PhMV particles against prostate cancer, ovarian and breast cancer cell lines, respectively. Our results show that PhMV-derived VLPs provide a new platform technology for the delivery of imaging agents and drugs, with preferential uptake into cancer cells. These particles could therefore be developed as multifunctional tools for cancer diagnosis and therapy.

Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery.

Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (e.g., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated Escherichia coli. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (i.e., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This in vitro model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in in vitro disease models (e.g., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body.

Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with controllable surface roughness for blood brain barrier transportation.

Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor.

Supramolecular Polymer Dot Ensemble for Ratiometric Detection of Lectins and Targeted Delivery of Imaging Agents.

A supramolecular, polymer-dot-based ensemble has been developed for the ratiometric detection of lectins and targeted delivery of glycoprobes. Self-assembly between a blue-emitting polymer dot and a red-emitting glycoprobe, results in an ensemble that shows red emission upon excitation of the polymer dot because of Förster resonance energy transfer. Resulting in ratiometric detection of lectins in buffer solution as well as targeted delivery of the glycoprobe to cells that highly express a sugar receptor. Unlike conventional systems where both the agent and vector are codelivered intracellularly, our ensemble developed here shows a receptor-controlled dissociation on the cell membrane.

Folate-Binding Protein Self-Aggregation Drives Agglomeration of Folic Acid Targeted Iron Oxide Nanoparticles.

Folate-conjugated nanomaterials have been widely investigated for drug and imaging-agent delivery. In this work, two folic acid (FA) conjugated iron oxide particles (IOP), a ∼40 nm diameter FA-IOP and a ∼450 nm diameter FA-IOP(FA-SeraMag), were synthesized. Both particles aggregated in the presence of serum folate-binding protein (FBP) at physiological concentration and buffer conditions. Mixing 0.01% w/w FA-conjugated iron oxide particles with FBP-induced agglomeration generated an average hydrodynamic particle diameter of 3800 ± 1100 nm for ∼40 nm FA-IOP and 4030 ± 1100 nm for FA-SeraMag as measured by dynamic light scattering (DLS). The presence of excess human serum albumin (HSA) (600 μM) did not prevent agglomeration of the ∼40 nm FA-IOP; however, it did inhibit agglomeration of FA-SeraMag. Atomic force microscopy measurement provided additional insight into particle morphology with the detection of individual particles in the agglomerate. This behavior is an example of a triggered cascade. A protein structural change is induced by FA binding, and the structural change favors aggregation of the ∼4 nm diameter FBPs on the particle surface; this further triggers the agglomeration of both the ∼40 and ∼450 nm diameter IOPs.

Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood–brain barrier and targeted fluorescence imaging of glioma and tumor vasculature

Delivery of imaging agents to brain glioma is challenging because the blood–brain barrier (BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots (QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides (NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH (4.0~8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo, contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine.

Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of α3 integrin-expressing human tumors.

Backgroundα3β1 integrin is overexpressed in several types of human cancer and is associated with poor prognosis, metastasis, and resistance to cancer treatment. We previously identified a cyclic peptide ligand LXY1 that specifically binds to the α3β1 integrin on human glioblastoma U-87MG cells. Here, we optimized LXY1 through one-bead one-compound combinatorial library screening and site-specific modifications to improve its in vivo binding property.MethodsThree bead libraries were synthesized and whole-cell binding assays were performed. The binding capacity of individual peptide ligands against different tumor cells was determined by flow cytometry and confirmed by optical imaging. A complex joining biotinylated ligand with streptavidin-Cy5.5 was used for in vivo target imaging in both subcutaneous and orthotopic U-87MG xenograft mouse models.ResultsLXY30, a cyclic peptide with the sequence cdG-Phe(3,5-diF)-G-Hyp-NcR, emerged as the most potent and selective ligand for the α3 subunit of α3β1 integrin with improved in vitro and in vivo tumor-targeting effects compared to LXY1 in U-87MG cells. LXY30 is considerably stable in plasma as demonstrated in an in vitro stability study in 90 % human plasma. LXY30 also binds to several other known α3β1 integrin-expressing glioblastoma, lung, and breast cancer cell lines with various affinities.ConclusionsOur data support further investigating the role of LXY30 as a human tumor-targeting peptide ligand for systemic and intracranial delivery of imaging agents and cancer therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0165-z) contains supplementary material, which is available to authorized users.

Simultaneous size and density determination of polymeric colloids by continuous contrast variation in small angle X-ray scattering

Polymeric colloids are of growing importance in nanomedicine for drug or imaging agent delivery. Their characterization is a crucial task but their traceable size determination is challenging, especially for particles with a complicated inner structure. This work describes the simultaneous determination of the size distribution and the density of polymeric particles by means of continuous contrast variation in small angle X-ray scattering (SAXS), which also reveals the inner structure of the colloids. The applicability of the technique has been evaluated by the comparison with other techniques, with focus on differential centrifugal sedimentation (DCS) in terms of the measured density. A novel approach to DCS is presented, which employs two centrifuge setups to enable the density and size determination of particles with physical densities close to water.

SIRT and Its Unresolved Problems—Is Imaging the Solution? A Review

Selective Internal Radiation Therapy (SIRT) is used as a treatment option for unresectable liver tumors. In SIRT, microspheres, which have a radioactive substance as an integral component, are placed via image guided catheters into the hepatic artery. The ionizing radiation is directly delivered to the tumor. Currently used commercially available microspheres are based on Yttrium 90, a β-emitter, which has been shown to be safe and to produce good clinical results. The technical features of Y90, their applications and their limitations are presented. Image guidance and intraoperative depiction of Yttrium 90 microspheres are restricted, which is currently one of the main limitations in SIRT. Therapy planning and control is currently based on pre- and post-operative images to evaluate the placement of the microspheres respectively. Holmium 166, another possible nuclide integrated into the microspheres emits a higher amount of secondary γ-radiation (Bremsstrahlung) than Yttrium 90. This enables an improved depiction of the microspheres inside the patient during and immediately after application, but comes with other shortfalls. Imaging of delivery and verification of the microsphere placement could solve many of the identified problems with SIRT. The different technologies are reviewed and an outlook in future developments is given particularly on image guidance and therapy control.