European legal regulation of patents in the area of science and research Bioethics is an important part of law regulation in the medical field. According to the current state, bioethics is able to highlighted main issues, which are connected with medical research and suggest possible solution.This paper combines two controversial topics. First one is human embryonic stem cell research and second one is research on nanoparts and indicates Intelectual Property Law possibilities in this field. Paper is divided into two parts. First one deals with the legal regulation on research on embryo in the Czech Republic and in other states of The Western Europe. Main focus is based on patentability of research concerned with the human embryonic stem cells, which might have a great therapeutic potential but their preparation necessarily leads to the destruction of "human embryos". (HESC) Main concern is connected with regard to the European law and the current ground- breaking judgement, Brüstle v. Greenpeace eV. In mentioned judgment European Court of Justice held that after interpretation of the Directive on the legal protection of biotechnological inventions , it will not be able to grant a patent on research which led in the destruction of a human embryo. Paper also includes assessment of the attitude of the...

>Magister Scientiae - MSc / Cancer is one of the leading causes of death, worldwide. Mortality tolls are estimated to reach approximately 13.1 million in 2030. These statistics suggest that current therapeutic strategies are not effective. This is partly due to the fact that the drugs used in the treatment of cancer lack selectivity and specificity, which lead to undesirable side effects and reduced drug efficacy. There is therefore a need for alternative therapeutic approaches. In view of this, the therapeutic goal of chemotherapy has shifted towards targeted drug delivery systems, which have been successfully demonstrated using nanotechnology. The nano-based drug delivery vehicles that specifically target diseased cells are appealing as they could reduce drug toxicity towards healthy tissues and be more effective at lower dosages. The main aim of this study was to develop gold nanorods (AuNRs) capable of inducing cell death in cancer cells specifically. Selectivity of the AuNRs (denoted as AGK) for cancer cells was achieved by conjugating the AuNRs to a peptide (Adipose Homing Peptide or AHP) that has high affinity and specificity for a cell surface receptor (prohibitin or PHB) that is expressed on some cancer cells. Cell death was achieved through conjugating the AuNRs to a pro-apoptotic peptide, D(KLAKLAK)2. Spherical AuNPs (AuNSs) conjugated with AHP and D(KLAKLAK)2, capable of selectively inducing apoptosis in cancer cells that express PHB, was previously reported. However, in this study the AuNSs were replaced with AuNRs. AuNRs has the ability to absorb light in the near infrared (NIR) light spectrum and converts this light energy into heat. This property of AuNRs has been used in several studies to demonstrate the application of AuNRs for the treatment of cancer using photothermal therapy (PTT). Consequently, the AuNRs described in this study can also be used for PTT. These AuNRs can induce cell death through the target specific delivery of the pro-apoptotic peptide D(KLAKLAK)2 as well as through PTT. The study showed that three human cancer cell lines (PC-3, Caco-2 and U-87) express PHB. The cytotoxicity testing of AGK AuNPs on PC-3 cells showed that these AuNRs could induce apoptosis in these cells without exposure to a NIR light source. The study also shows that AuNRs conjugated with the targeting peptide only (denoted as AG) can induce cell death in Caco-2 through PTT. This study demonstrates the potential of the AuNRs described in this study for application in the targeted elimination of cancer cells through the selective induction of PTT and apoptosis.

No description available.

The construction of nanoscale polymeric objects with complex, well-defined structures and regiochemical functionalities is of great importance, because it enables the fabrication of soft materials with tunable properties. Direct polymerization of macromonomers through covalent bond formation and self-assembly of block copolymers via non-covalent interactions are two typical strategies to afford nanoscopic structures. Molecular brush polymers are composed of densely-grafted side chains along a polymeric backbone. Due to the significant steric repulsion from the side chains, they tend to adopt bottle-brush like conformations, as opposed to linear polymers. "Grafting through" synthesis of molecular brush polymers can provide precise control over the dimensions and functionalities of brush polymers. Shell crosslinked knedel-like nanoparticles (SCKs) are constructed by assembling from amphiphilic block copolymers into micelles, followed by covalent shell crosslinking to further stabilize the nanoparticles and introduce additional functional moieties. SCKs are attractive nanocarriers because of their variable morphologies, compositions and functionalities, which allow for the development of platforms for therapeutic or diagnostic purposes. By utilizing the orthogonal reactivity of the norbornene group and methacrylate group, two distinctly different reactive well-defined linear polymers, and a facile, one-pot synthesis of well-defined molecular brush polymers were studied by selective, orthogonal controlled radical polymerizations (CRPs) and ring-opening metathesis polymerization (ROMP). The living and high efficient characteristics of "grafting-through" strategy were further investigated for the preparation of topology-controlled brush polymers with tunable dimensions of both backbone and side chain lengths. Apart from the fundamental investigation of molecular brush polymers, a series of poly(carboxybetaine) (PCB)- and poly(ethylene glycol) (PEG)-grafted degradable SCKs were developed to evaluate their in vivo pharmacokinetics and biodistributions, aiming to achieve novel therapeutic and diagnostic platforms that may surpass the performance of the conventional PEGylated analogs.

Applications of nanotechnology in medicine, also known as nanomedicine, is a rapidly growing field as it holds great potential in the development of novel therapeutics toward treatment of various diseases. Shell crosslinked knedel-like nanoparticles (SCKs) that are self assembled from amphiphilic block copolymers into polymeric micelles followed by crosslinking selectively throughout the shell domain have been investigated as theranostic agents for the delivery of nucleic acids and incorporation of imaging probes. The main focus of this dissertation is to design and develop unique multifunctional bio-synthetic hybrid nanoparticles that can carry agents for radiolabeling, moieties for inducing stealth properties to minimize protein adsorption in vivo, ligands for site-specific targeting, therapeutic payloads, and are optimized for efficient delivery of cargoes intracellularly and to the target sites toward constructing novel nanoscopic objects for therapy and diagnosis. Alteration of polymeric building blocks of the nanoparticles provides opportunities for precise control over the sizes, shapes, compositions, structures and properties of the nanoparticles. To ensure ideal performance of nanoparticles as theranostic agents, it is critical to ensure high intracellular bioavailability of the therapeutic payload conjugated to nanoparticles. Special efforts were made by employing well-defined multi-step polymerization and polymer modification reactions that involved conjugation of peptide nucleic acids (PNAs) to chain terminus of poly(ethylene glycol) (PEG) chain grafts such that they were presented at the outermost surface of SCKs. Additionally, chemical modification reactions were performed on the polymer backbone to integrate positive charges onto the shell of the nanoparticles to afford cationic SCKs (cSCKs) for facilitating cellular entry and electrostatic interactions with negatively charged nucleic acids. Covalent conjugation of F3, a tumor homing peptide, post-assembly of the nanoparticles enhanced cellular uptake and knockdown of nucleolin (a shuttling protein overexpressed at the sites of angiogenesis) and thus inhibiting tumor cell growth. Furthermore, these polymer precursors of the cSCKs were modified with partial to full incorporation of histamines to facilitate their endosomal escape for efficient delivery into the cytosol. The cSCKs were further templated onto high aspect ratio anionic cylinders to form hierarchically-assembled nanostructures that bring together individual components with unique functions, such as one carrying a therapeutic payload and the other with sites for radiolabeling. These higher order nanoobjects enhance circulation in vivo, have capabilities to package nucleic acids electrostatically and contain sites for radiolabeling, providing an overall advantage over the individual components, which could each facilitate only one or the other of the combined functions. Hierarchically-assembled nanostructures were investigated for their cellular uptake, transfection behavior and radiolabeling efficiency, as the next generation of theranostic agents.

The field of structural DNA nanotechnology utilizes DNA's powerful base-pairing molecular recognition criteria to help solve real challenges facing researchers in material science and nanotechnology, some of which include synthesis, sensing, catalysis, delivery, storage, optics, electronics, and scaffolding. In it, DNA is stripped away from any of its preconceived biological roles, and is treated as a powerful synthetic polymer. A subarea of research that our group has recently termed supramolecular DNA nanotechnology is emerging, and is proving to be a powerful complement to some of the already established rules of structural DNA nanotechnology. The work within this thesis falls under the umbrella of supramolecular DNA nanotechnology, and can conceptually be divided into three parts. (1) The first deals with the problem of discrete nanopartic1e organization. In it we present an approach for the facile and economical access to libraries of discrete nanoparticle assemblies that are addressable and switchable post-assembly. (2) The second deals with the synthesis of three-dimensional DNA assemblies. In it we present an approach for the facile construction of discrete three-dimensional DNA cages that can be structurally oscillated between pre-defined lengths, and adapt this approach to generate geometrically well-defined DNA columns of modular stiffness. (3) The last part deals with the use of small molecules to reprogram the assembly behavior of DNA. In it we use molecules to address the issue of error-correction, during and after the assembly process, and to facilitate the synthesis of "higher-order" DNA helices composed of more than two DNA strands. This work collectively offers a set of simple solutions to some of the bigger challenges currently facing researchers in DNA nanotechnology, and provides a snapshot of what is to be expected from tehe emerging discipline that is supramolecular DNA nanotechnology.

Porphyrins are naturally occurring molecules. Porphysomes are simple multimodal nanoparticles that derive their multifunctionality from porphyrin-based building-blocks. While previous studies have probed their interactions with light, their capacity to stably chelate metal ions has gone largely uninvestigated. Herein are presented and discussed two investigations into metalloporphysomes. First is a method for non-invasively labeling porphysomes with radioactive copper-64. Utilizing exceptionally simple chemistry, this method produces a highly stable radiotracer capable of both PET and fluorescence imaging. Second is a profile of a MRI-detectable, photothermal agent whose photonic properties are serendipitously improved by the incorporation of MRI-active metal ions. By taking advantage of simple chemical substitutions, these studies illustrate methods of accessing new functionalities while maintaining a deeply simple construct, an often overlooked aspect in the development of multimodal nanoparticles.

No description available.

Porphyrins are naturally occurring molecules. Porphysomes are simple multimodal nanoparticles that derive their multifunctionality from porphyrin-based building-blocks. While previous studies have probed their interactions with light, their capacity to stably chelate metal ions has gone largely uninvestigated. Herein are presented and discussed two investigations into metalloporphysomes. First is a method for non-invasively labeling porphysomes with radioactive copper-64. Utilizing exceptionally simple chemistry, this method produces a highly stable radiotracer capable of both PET and fluorescence imaging. Second is a profile of a MRI-detectable, photothermal agent whose photonic properties are serendipitously improved by the incorporation of MRI-active metal ions. By taking advantage of simple chemical substitutions, these studies illustrate methods of accessing new functionalities while maintaining a deeply simple construct, an often overlooked aspect in the development of multimodal nanoparticles.

Decreasing the number of people that die from preventable illnesses and reducing poverty and inequality are major public goods that are being addressed from a variety of angles. One way that policy makers and scholars are trying to improve global health is by developing new health technologies that will decrease poverty and inequality. This dissertation investigates whether nanotechnologies for medical applications (nanomedicine) are used to address diseases of poverty (DoP) and the role that public partnerships (PPP) play in nanomedicine research. If scientists are developing nanotechnology based vaccines and medicines for DoP, then I can conclude that the technology is helping to decrease poverty and inequality. There are two parts to my analysis. The first part of my dissertation analyses the landscape of nanomedicine DoP research and then I test how USA medicine sales, disease burden and diseases of poverty correlate with number of nanomedicine publications and patents. I find that there is some nanomedicine research on diseases of poverty, especially for high profile DoP like malaria, tuberculosis and HIV/AIDS, but overall there is less R&D on DoPs than non-DoPs. However, I cannot determine if USA medicine sales and disease burden have any relationship to research output. In the second part of my dissertation I examine the role of formal public-private partnerships (PPPs) for developing DoP medicines. Many think the formal health PPPs can overcome the various market failures associated with developing medicines for DoP. I analyze PPP websites and interview PPP managers/scientists about their research portfolios, relationship with nanotechnology, and how PPPs are addressing inequality in health R&D. I find that managers/scientists at PPPs have a variety of opinions about nanotechnology, but the general consensus is that nanotechnology will not be used in the near-term for DoP medicines. PPP managers/scientists believe that the technology is too expensive for DoP medicines and it will take too long to approve nanomedicines. Instead of using nanotechnology most PPPs are in favor of using traditional technologies.