Nanoengineering of Exosomal Surfaces for Precision Targeting and Payload Delivery at the Molecular Level.

Positron emission tomography is one of the most important tools in medical imaging with many applications in neurology, oncology, cardiology, neuroscience, and infection. Over the past 40 years, technological advances in radiochemistry have led to the development of many radiotracers at the present used in clinical routine.In this chapter we will discuss the main physical property of PET radionuclide and the main pharmacokinetic characteristics of PET radiotracers commonly used in the clinical routine for molecular imaging.KeywordsPositron emission tomography radiopharmaceuticalsPET tracersPET radionuclides

Positron Emission Tomography, which is a functional imaging technique, measures in three-dimension the bio-distribution of a radiotracer in a specific organ or tissue. Thanks to tracer characteristics, the PET imaging was successfully experimented into several applications in oncology, cardiology and neurology for clinical and research trials. The segmentation of PET image is a mandatory step in all PET applications since it allows to relay imaged tracer uptake within a region of interest to its underlying biology. However, manual segmentation was limited by its time consuming, labor intensive and its high intra- and inter-operator variability. Therefore, several automated PET image segmentation methods were developed. In this paper, we presented the most relevant methods in the literature including thresholding-based methods of static PET images, deformable models for cardiac PET studies and mono and multi-modal segmentation methods for brain PET images. Keywords: Cardiology, deformable models, multi-modal segmentation, neurology, oncology, PET image, thresholding-based segmentation.

During the past decade, systems biology and synthetic biology have emerged as two new subdisciplines of biology. Although seemingly disparate, there are distinct overlaps that are worth exploring, particularly in terms of the origin of life. Systems biology is guided by the growing understanding that most cellular processes occur in the form of networks controlled by sensors, signals and effectors—properties that find analogies in electronic control systems. A few important life processes could even be characterized as digital, such as the genetic code, ribosome function and the on–off firing of action potentials in neurons. Systems biologists now try to embed these processes in computational models that could provide predictive insights into biological processes at the cellular level. By contrast, other important cellular functions occur through spontaneous self‐assembly processes that are not under precise regulatory control, such as the insertion of lipids and certain proteins into membranes. Most other regulatory signals are essentially diffusion processes that exert their effects by summation over time and space. This includes, for example, the diffusion of ions through channels to produce the resting and action potentials of individual neurons, the diffusion of neurotransmitters across the synaptic cleft and the diffusion of growth factors that govern the differentiation of cells into specific tissues within the developing embryo. These regulatory functions are not in any sense digital, although they work well—indeed, life depends on them. The origin of life therefore clearly illustrates how a living system can emerge from a chaotic environment in the absence of anything that could be called digital control. Instead, the origin of life is better understood in terms of synthetic biology, which is currently defined in engineering terms with a primary goal of developing a 'toolkit' that will make it possible to manipulate the genetic blueprint of living cells. The main point …

Preface

For the purpose of constructing or generating new life forms, synthetic biology is a multidisciplinary field that blends biology with engineering, physics, mathematics, chemistry, and computer science. Making Biobricks, designing metabolic pathways, whole-genome synthesis, protocell engineering, and Xenobiology are the primary synthetic biology techniques. Synthetic biology spans a variety of industries, including pharmaceuticals, energy, chemicals, biosensors, and environmental protection. Although it has various uses, there are risk issues with biosafety, biosecurity, and bioethics. Strong regulatory rules must be developed in order to increase the risks associated with sedentary behavior. The Cartagena protocol recognizes some synthetic biology applications and outcomes as living modified organisms. The protocol's advance informed agreement governs the trans-boundary transfer of living, synthetically modified organisms. Dual-use technologies are governed by laws agreed under the Biological Weapons Convention and relate to synthetic biology products. Synthetic biology also makes use of the Nagoya Protocol, trade-relevant IP rights, and other legislative frameworks. However, because synthetic biology is a young field of study, there are no explicit regulations governing it in any way under international law. The purpose of this review is to evaluate the regulatory regulations governing synthetic biology and to describe the applications and hazards of synthetic biology.

We have conducted a stability study of a complex liposomal pharmaceutical product, Atheroglitatide (AGT), stored at three temperatures, 4, 24, and 37 °C, for up to six months. The six parameters measured were functions of liposomal integrity (size and number), drug payload (loading efficiency), targeting peptide integrity (conjugation efficiency and specific avidity), and echogenicity (ultrasound-dependent controlled drug release), which were considered most relevant to the product’s intended use. At 4 °C, liposome diameter trended upward, indicative of aggregation, while liposome number per mg lipid and echogenicity trended downward. At 24 °C, peptide conjugation efficiency (CE) and targeting efficiency (TE, specific avidity) trended downward. At 37 °C, CE and drug (pioglitazone) loading efficiency trended downward. At 4 °C, the intended storage temperature, echogenicity, and liposome size reached their practical tolerance limits at 6 months, fixing the product expiration at that point. Arrhenius analysis of targeting peptide CE and drug loading efficiency decay at the higher temperatures indicated complete stability of these characteristics at 4 °C. The results of this study underscore the storage stability challenges presented by complex nanopharmaceutical formulations.

Readily Accessible Bicyclononynes for Bioorthogonal Labeling and Three‐Dimensional Imaging of Living Cells

Positron emission tomography is a rapidly growing field of clinical nuclear medicine with most frequent applications in oncology and less frequent applications in cardiology and neurology. Recent developments have resulted in instruments that can image the whole body within 10-15 minutes, at a spatial resolution of 5-6 mm and counting sensitivities of 30 cps/Bq/ml.1 The advantage of PET is that the images are readily corrected for radioisotope decay, radiopharmaceutical dose, tissue attenuation and scatter. The concentration of the radiopharmaceutical can be calibrated and displayed in MBq/ml, kBq/ml/MBq injected dose or mEq/ml. These properties of PET make quantification of renal blood flow and glomerular filtration rate (GFR) straightforward and also make imaging of molecular targets including enzymes and receptors of the kidneys possible. Despite the many advantages, clinical applications of PET are still in their early development.

Even though combined PET/CT scanners have been in production for only 4 years, the technology is undergoing rapid evolution. For PET, the introduction of new scintillator materials, detector concepts, and electronics is resulting in performance improvements in count rate, spatial resolution, and signal-to-noise. At the same time, the increasing number of detector rows and reduction in rotation time are transforming whole-body CT performance. The combination of high-performance CT with high-performance PET is a powerful imaging platform for the diagnosis, staging, and therapy monitoring of malignant disease. Although the PET scanners incorporated into current PET/CT designs are still offered by some vendors for PET-only applications, more than 95% of PET sales are now PET/CT, and the likelihood is that PET-only scanners will be replaced entirely by PET/CT in the future. It is expected that there will then be a demand for a design that offers less performance at less cost. To meet this demand, an entry-level or midrange PET/CT is required, possibly in a form similar to the original prototype with PET detectors mounted on the same rotating assembly as the CT. Because the performance of the PET components is the limitation on the overall imaging time, institutions requiring high throughput and large patient volumes will always demand the highest PET performance. Nevertheless, a 6- or 8-slice CT scanner should be adequate for most oncology applications, with a 16- or 64- slice CT appropriate for PET/CT applications in cardiology. As the current PET/CT technology becomes more widespread, appropriate future designs of this concept will doubtless emerge.

Combined PET-CT scanners have been in production for over 10 years, and the technology has undergone rapid evolution. For PET, the introduction of new scintillator materials, detector concepts, and electronics is resulting in performance improvements in count rate, spatial resolution, and signal-to-noise. At the same time, the increasing number of detector rows and reduction in rotation time are transforming whole-body CT performance. The combination of high performance CT with high performance PET is a powerful imaging platform for the diagnosis, staging and therapy monitoring of malignant disease. A 16-slice CT scanner should be adequate for most oncology applications, with a 64- or 128-slice CT more appropriate for PET-CT applications in cardiology. As the current PET-CT technology becomes more widespread, appropriate future designs of this concept will doubtless emerge.

Bioorthogonal SERS-bioluminescence dual-modal imaging for real-time tracking of triple-negative breast cancer metastasis.

Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.

Affibody Molecules in Biotechnological and Medical Applications

Chapter 1: Introduction (Pengcheng Fu). Chapter 2: Basics of Molecular Biology, Genetic Engineering and Metabolic Engineering (Michael X. Wang and Huidong Shi). Chapter 3: High-Throughput Technologies and Functional Genomics (Henry Wang and Dorothea K. Thompson). Chapter 4: Predicting the Lymph Node Status of Breast Cancer Tumors Using Gene Expression Patterns and Genomic Signal Processing (Gordon Okimoto). Chapter 5: From Recombinant Genes to Recombinant Genomes for Systems Biology (Mitsuhiro Itaya). Chapter 6: In silico Genome-scale Metabolic Models: The Constraint-based Approach and its Applications (Andrew Joyce and Bernhard Palsson). Chapter 7: Mathematical Modeling of Genetic Regulatory Networks: Stress Responses in Escherichia coli (Delphine Ropers, Hidde de Jong, and Johannes Geiselmann). Chapter 8: Systems Approaches in Molecular Diagnostics and Drug Development (Martin Latterich). Chapter 9: Yeast as a Prototype for Systems Biology (Gautham Vemuri and Jens Nielsen). Chapter 10: Construction and Applications of Genome-Scale In Silico Metabolic Models for Strain Improvement (Sang Yup Lee, Jin Sik Kim, Hongseok Yun, Tae Yong Kim, Seung Bum Sohn, Hyun Uk Kim). Chapter 11: Synthetic Biology: Putting Engineering into Bioengineering (Matthias Heinemann and Sven Panke). Chapter 12: Rationals of Gene Design and de novo Gene Construction (Marcus Graf, Thomas Schoedl and Ralf Wagner). Chapter 13: Self-replication in Chemistry and Biology (Phil Holliger and David Loakes). Chapter 14: The Synthetic Approach for Regulatory and Metabolic Circuits (Wilson W. Wong and James C. Liao). Chapter 15: Synthetic Genetic Networks (David Greber and Martin Fussenegger). Chapter 16: The theory of biological robustness and its implication to cancer (Hiroaki Kitano). Chapter 17: Nucleic Acid Engineering (Wenlong Cheng, Liang Ding, Hisakage Funabashi, Nokyoung Park, Soong Ho Um, Jianfeng Xu, and Dan Luo). Chapter 18: Potential Applications of Synthetic Biology in Marine Microbial Functional Ecology and Biotechnology (Guangyi Wang and Juanita Mathews). Chapter 19: On fundamental implications of systems and synthetic biology (Cliff Hooker). Chapter 20: Outstanding Issues in systems and synthetic biology (Pengcheng Fu and Cliff Hooker).

Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics