Bioorthogonale Ligationsreaktionen an Grenzflächen

In dieser Arbeit werden verschiedene Synthesestrategien beschrieben, welche Zugang zu einer Substanzbibliothek neuer polyvalenter Strukturen ermöglicht, die sich durch ein breites Spektrum an funktioneller Vielfalt auszeichnet, sowie deren Anwendungen in der Herstellung von Biomaterialien

Multifunctional nanoparticles for specific neuroblastoma targeting

Neuroblastoma is a solid extracranial cancer of the nervous system. Besides leukemia, brain tumors, and central nervous system tumors, neuroblastoma is the most common cancer in children.1 It mainly affects children under 15 years old and accounts for 15% of childhood cancer deaths.2 There is a wide variety of treatment options for neuroblastomas; ranging from surgery or chemotherapy in children with low-risk to medium-risk forms of the disease, to aggressive multimodal therapies in patients with high-risk forms.3 A treatment used in certain high-risk patients is iodine-131 meta-iodobenzylguanidine (I-131 MIBG) radiotherapy. MIBG is a norepinephrine analogue that localizes to adrenergic cells. Neuroblastoma cells overexpress adrenergic receptors, and thus take up MIBG at higher rates than other tissues.4 Because of this, when modified with I-131, MIBG is used as a radiotherapy agent.5 I-131 MIBG treatment, as a highly specific therapy, avoids many of the heavy side effects seen in other cancer treatments, but its radioactivity causes a need for highly specialized facilities. Additionally, all patients undergoing I-131 MIBG treatment must remain in isolation for several days while radiation in their system is reduced to safe levels, which is especially difficult for children. As an alternative to I-131 MIBG treatment, a nanoparticle (NP) system that uses MIBG to home to neuroblastoma cells and then releases chemotherapy agents in their immediate vicinity may result in a better treatment for the disease. It would be more patient friendly in that, in addition to the above stated advantages of MIBG, it would contain no radioactive properties and therefore avoid the need for patient isolation and specialized facilities, which would increase patient compliance and reduce costs. Similar NPs were previously shown to be useful for drug loading purposes and therapeutic release rates can be controlled in NP systems, as opposed to the traditional therapy.6 Through electrohydrodynamic (EHD) co-jetting, our group has fabricated surface modifiable, biodegradable nanoparticles that can be used for predictable, controlled, and distinct delivery of therapeutics.7 In this work we present the fabrication poly-lactic-glycolic acid NPs chemically modified to display MIBG on their surface that were manufactured using our EDH methodology. We characterized the system using proton nuclear magnetic resonance, scanning electron microscopy, dynamic light scattering, and nanoparticle tracking analysis. Increased particle uptake for MIBG modified NPs vs controls in a neuroblastoma line was observed using confocal microscopy and flow cytometry. Future work will investigate the efficacy of these particles for delivering chemotherapeutics in in-vitro and in-vivo systems based on previously published work on drug loading studies in our group.8 1. Pizzo, P. A. & Poplack, D. G. Principles and practice of pediatric oncology. (2006). 2. Stiller, C. A. & Parkin, D. M. International variations in the incidence of neuroblastoma. Int. J. Cancer 52, 538–543 (1992). 3. Park, J. R., Eggert, A. & Caron, H. Neuroblastoma: Biology, Prognosis, and Treatment. Hematol. Oncol. Clin. North Am. 24, 65–86 (2010). 4. Hattner, R. S., Huberty, J. P., Engelstad, B. L. & Gooding, C. A. Localization of m-lodo (I-131) benzylguanidine Neuroblastoma. 373–374 (1984). 5. Riad, R. et al. Role of 131-I MIBG Therapy in the Treatment of Advanced Neuroblastoma. J. Egypt. Natl. Canc. Inst. 21, 51–8 (2009). 6. Rahmani, S., Park, T. H., Dishman, A. F. & Lahann, J. Multimodal delivery of irinotecan from microparticles with two distinct compartments. J. Control. Release 172, 239–245 (2013). 7. Rahmani, S. & Lahann, J. Recent progress with multicompartmental nanoparticles. MRS Bull. 39, 251–257 (2014). 8. Rahmani, S. et al. Dual Release Carriers for Cochlear Delivery. Adv. Healthc. Mater. 5, 94–100 (2016)

Hierarchically Functionalized Magnetic Core/Multishell Particles and Their Postsynthetic Conversion to Polymer Capsules

The controlled synthesis of hierarchically functionalized core/multishell particles is highly desirable for applications in medicine, catalysis, and separation. Here, we describe the synthesis of hierarchically structured metal–organic framework multishells around magnetic core particles (magMOFs) <i>via</i> layer-by-layer (LbL) synthesis. The LbL deposition enables the design of multishell systems, where each MOF shell can be modified to install different functions. Here, we used this approach to create controlled release capsules, in which the inner shell serves as a reservoir and the outer shell serves as a membrane after postsynthetic conversion of the MOF structure to a polymer network. These capsules enable the controlled release of loaded dye molecules, depending on the surrounding media

Fabrication of Highly Uniform Gel Coatings by the Conversion of Surface-Anchored Metal–Organic Frameworks

We report the fabrication of 3D, highly porous, covalently bound polymer films of homogeneous thickness. These surface-bound gels combine the advantages of metal–organic framework (MOF) materials, namely, the enormous flexibility and the large size of the maximum pore structures and, in particular, the possibility to grow them epitaxially on modified substrates, with those of covalently connected gel materials, namely, the absence of metal ions in the deposited material, a robust framework consisting of covalent bonds, and, most importantly, pronounced stability under biological conditions. The conversion of a SURMOF (surface-mounted MOF) yields a surface-grafted gel. These SURGELs can be loaded with bioactive compounds and applied as bioactive coatings and provide a drug-release platform in in vitro cell culture studies