Protecting redesigned supercharged ferritin containers against protease by integration into acid-cleavable polyelectrolyte microgels.

HYPOTHESIS: The application of ferritin containers as a promising drug delivery vehicle is limited by their low bioavailability in blood circulation due to unfavorable environments, such as degradation by protease. The integration of ferritin containers into the polymeric network of microgels through electrostatic interactions is expected to be able to protect ferritin against degradation by protease. Furthermore, a stimuli-responsive microgel system can be designed by employing an acid-degradable crosslinker during the microgel synthesis. This should enable ferritin release in an acidic environment, which will be useful for future drug delivery applications. EXPERIMENTS: Nanoparticle/fluorophores-loaded ferritin was integrated into microgels during precipitation polymerization. The integration was monitored by transmission electron microscopy (TEM)2 and fluorescence microscopy, respectively. After studying ferritin release in acidic solutions, we investigated the stability of ferritin inside microgels against degradation by chymotrypsin. FINDINGS: About 80% of the applied ferritin containers were integrated into microgels and around 85% and 50% of them could be released in buffer pH 2.5 and 4.0, respectively. Total degradation of the microgels was not achieved due to the self-crosslinking of N-isopropylacrylamide (NIPAM). Finally, we prove that microgels could protect ferritin against degradation by chymotrypsin at 37 °C.

Continuous hyperpolarization with parahydrogen in a membrane reactor.

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the "Signal Amplification by Reversible Exchange" (SABRE) approach uses para-enriched hydrogen, p-H2, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H2, supply and consecutive detection in a 1 T NMR spectrometer. Two SABRE substrates pyridine and nicotinamide were hyperpolarized, and more than 1000-fold signal enhancement was found. Our strategy combines low-field NMR spectrometry and a membrane flow reactor. This enables precise control of the experimental conditions such as liquid and gas pressures, and volume flow for ensuring repeatable maximum polarization.

Hyperpolarizing Water with Parahydrogen.

Studies of water-based systems are of fundamental interest for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) as water is the most abundant and important medium for global living. Hence, increasing the polarization of water and dissolved compounds is particularly attractive for biomedical applications such as investigations of intermolecular interactions and metabolite structures as well as for imaging purposes. In this work, we show a new approach based on para enriched hydrogen (p-H2 ) that enables the hyperpolarization of bulk water if a suitable catalytic system is employed. The results indicate that the polarization is transferred by a new exchange mechanism.