Enhancing NMR signals of biomacromolecules by hyperpolarization offers exciting opportunities for diagnostic applications. However, their hyperpolarization via parahydrogen remains challenging as specific catalytic interactions are required, which are difficult to tune due to the large size of the biomolecule and its insolubility in organic solvents. Herein, we show the unprecedented hyperpolarization of the cancer-targeting DNA aptamer AS1411. By screening different molecular motifs for an unsaturated label in nucleosides and in DNA oligomers, we were able to identify structural prerequisites for the hyperpolarization of AS1411. Finally, adjusting the polarity of AS1411 by complexing the DNA backbone with amino polyethylene glycol chains allowed the hydrogenation of the label with parahydrogen while the DNA structure remains stable to maintain its biological function. Our results are expected to advance hyperpolarized molecular imaging technology for disease detection in the future.

In pH‐responsive drug carriers, the distribution of charges has been proven to affect delivery efficiency but is difficult to control and verify. Herein, we fabricate polyampholyte nanogel‐in‐microgel colloids (NiM−C) and show that the arrangement of the nanogels (NG) can easily be manipulated by adapting synthesis conditions. Positively and negatively charged pH‐responsive NG are synthesized by precipitation polymerization and labelled with different fluorescent dyes. The obtained NG are integrated into microgel (MG) networks by subsequent inverse emulsion polymerization in droplet‐based microfluidics. By confocal laser scanning microscopy (CLSM), we verify that depending on NG concentration, pH value and ionic strength, NiM−C with different NG arrangements are obtained, including Janus‐like phase‐separation of NG, statistical distribution of NG, and core–shell arrangements. Our approach is a major step towards uptake and release of oppositely charged (drug) molecules.

Die Verteilung von Ladungen innerhalb pH‐responsiver Wirkstoffträger beeinflusst nachweislich die Effizienz der Freisetzung, ist aber schwer zu kontrollieren und zu verifizieren. Wir stellen nun polyampholytische Nanogel‐in‐Mikrogel Kolloide (NiM−C) vor und zeigen, dass die Anordnung der Nanogele (NG) abhängig von den Synthesebedingungen ist. Dazu wurden pH‐responsive Polyelektrolyt‐NG durch Fällungspolymerisation synthetisiert und mit Fluoreszenzfarbstoffen markiert. Die NG wurden dann durch inverse Emulsionspolymerisation mittels tropfenbasierter Mikrofluidik in Mikrogel‐Netzwerke (MG) integriert. Mit konfokaler Laser‐Scanning‐Mikroskopie (CLSM) wurde nachgewiesen, dass, je nach NG‐Konzentration, pH‐Wert und Ionenstärke, NiM−C mit unterschiedlichen NG‐Anordnungen, wie Janus‐artiger Phasentrennung, statistischer Verteilung und Kern‐Schale‐Architektur, erhalten werden. Unser Ansatz ist ein Meilenstein auf dem Weg zum simultanen Transport entgegengesetzt geladener Moleküle.