Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward

Reversible Addition Fragmentation Chain Transfer Polymerization of Water-Soluble, Ion-Containing Monomers

Reversible add ition-fragmentation chain transfer (RAFT) polymerization has been the focus of extensive research over the last several years. RAFT allows for the tailoring of polymers with complex architectures including block, graft, comb, and star structures with predetermined molecular weights, end group functionality, and narrow molecular weight distributions. In this chapter we present an overview of the synthesis and solution properties of water-soluble, ioncontaining monomers synthesized via RAFT

Swelling Behavior and Nanomechanical Properties of (Peptide-Modified) Poly(2-hydroxyethyl methacrylate) and Poly(poly(ethylene glycol) methacrylate) Brushes

Poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(poly(ethylene glycol) methacrylate) (PPEGMA) brushes represent a class of thin, surface-tethered polymer films that have been extensively used e.g. to generate non-biofouling surfaces or as model systems to study fundamental biointerfacial questions related to cell–surface interactions. As the properties of PHEMA and PPEGMA brushes depend on the hydration and swelling of these thin films, it is important to understand the influence of basic structural parameters such as the composition of the polymer brush, the film thickness, or grafting density on these phenomena. This article reports results of a series of experiments that were performed to investigate the swelling behavior and mechanical properties of a diverse library of PHEMA and PPEGMA brushes covering a range of film thicknesses and grafting densities. The swelling ratios of the PHEMA and PPEGMA brushes were determined by ellipsometry and neutron reflectivity experiments and ranged from ∼1.5 to ∼5.0. Decreasing the grafting density and decreasing the film thickness generally results in an increase in the swelling ratio. Modification of the PHEMA and PPEGMA brushes with the cell adhesive RGD peptide ligand was found to result in a decrease in the swelling ratio. The neutron reflectivity experiments further revealed that solvated PHEMA and PPEGMA brushes are best described by a two-layer model, consisting of a polymer-rich layer close to the substrate and a second layer that is swollen to a much higher degree at the brush–water interface

Aqueous RAFT Polymerization of Acrylamide and N,N-Dimethylacrylamide at Room Temperature

The first example of a room temperature reversible addition fragmentation chain transfer polymerization conducted directly in aqueous media is detailed. Under these conditions acrylamide and N,N-dimethylacrylamide may be polymerized in a controlled fashion to near quantitative conversions employing a difunctional trithio-carbonate chain transfer agent (CTA). Hydrolysis studies conducted at pH 5.5 suggest that the CTA is stable up to approximately 50 degrees C

Aqueous RAFT Polymerization of Acrylamide and N,N-Dimethylacrylamide At Room Temperature

The first example of a room temperature reversible addition-fragmentation chain transfer polymerization conducted directly in aqueous media is detailed. Under these conditions acrylamide and N,N-dimethylacrylamide may be polymerized in a controlled fashion to near quantitative conversions employing a difunctional trithiocarbonate chain transfer agent (CTA). Hydrolysis studies conducted at pH 5.5 suggest that the CTA is stable up to approximately 50°C

Direct Synthesis of Thermally Responsive DMA/NIPAM Diblock and DMA/NIPAM/DMA Triblock Copolymers Via Aqueous, Room Temperature RAFT Polymerization

We report aqueous, room temperature RAFT polymerization of N-isopropylacrylamide (NIPAM) and, subsequently, its block copolymerization utilizing a poly(N,N-dimethylacrylamide) macro-CTA. A series of thermally responsive AB diblock and ABA triblock copolymers have been prepared. These polymers contain hydrophilic N,N-dimethylacrylamide (DMA) A blocks of fixed molecular weight and temperature-responsive NIPAM B blocks of varied chain length. Using a combination of 1H NMR spectroscopy, T2 relaxation measurements, dynamic light scattering (DLS), and static light scattering (SLS), we demonstrate that these block copolymers are indeed capable of reversibly forming micelles in response to changes in solution temperature and that the micellar size and transition temperature are dependent on both the NIPAM block length and the polymer architecture (diblock vs triblock)

Search for parity violation in 93Nb neutron resonances

A new search has been performed for parity violation in the compound nuclear states of 94Nb by measuring the helicity dependence of the neutron total cross section. Transmission measurements on a thick niobium target were performed by the time-of-flight method at the Manuel Lujan Neutron Scattering Center with a longitudinally polarized neutron beam in the energy range 32 to 1000 eV. A total of 18 p-wave resonances in 93Nb were studied with none exhibiting a statistically significant parity-violating longitudinal asymmetry. An upper limit of 1.0× 10-7 eV (95% confidence level) was obtained for the weak spreading width Γw in 93Nb