Nanogels open up access to a wide range of applications and offer among others hopeful approaches for use in the field of biomedicine. This review provides a brief overview of current developments of nanogels in general, particularly in the fields of drug delivery, therapeutic applications, tissue engineering, and sensor systems. Specifically, cyclodextrin (CD)‐based nanogels are important because they have exceptional complexation properties and are highly biocompatible. Nanogels as a whole and CD‐based nanogels in particular can be customized in a wide range of sizes and equipped with a desired surface charge as well as containing additional molecules inside and outside, such as dyes, solubility‐mediating groups or even biological vector molecules for pharmaceutical targeting. Currently, biological investigations are mainly carried out in vitro, but more and more in vivo applications are gaining importance. Modern molecular imaging methods are increasingly being used for the latter. Due to an extremely high sensitivity and the possibility of obtaining quantitative data on pharmacokinetic and pharmacodynamic properties, nuclear methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiolabeled compounds are particularly suitable here. The use of radiolabeled nanogels for imaging, but also for therapy, is being discussed.

Stable water-in-oil emulsion membranes can be prepared using [dilauryl(dimethyl)ammonium] bromide (DDAB), a cationic surfactant. We prepared ultrasmall cyclodextrin (γ-CyD) nanogels (γ-CyDngs) by forming ionic pairs between the secondary hydroxyl groups of γ-CyDs and DDAB. Fluorescence and NMR characterisation of the obtained γ-CyDngs revealed superior inclusion affinities compared with native γ-CyDs, beneficial for the solubilisation of hydrophobic compounds in water.

Various diboronic acid-based chemosensors for D-glucose have been developed for use in diabetes diagnostic systems. However, most of these chemosensors have limitations, such as poor water solubility, difficulties in synthesis, and inability to selectively detect D-glucose from among other saccharides. We report a simple chemosensor based on a supramolecular complex of fluorophenylboronic acid-appended β-cyclodextrin (FPB-βCyD) and an anthracene-based probe having a boronic acid moiety (1). Hydrophobic 1 is encapsulated in the cyclodextrin cavity of FPB-βCyD, making the supramolecular complex (1/FPB-βCyD) applicable in a water-rich solvent mixture (98% water). Interestingly, 1/FPB-βCyD showed a strong turn-on response to D-glucose with a 9.6-fold enhancement in fluorescence intensity, and no response to other saccharides. This study uncovers an innovative approach based on the supramolecular assembly of simple components for the development of a water-soluble D-glucose chemosensor with excellent selectivity.

Various organic compound-based chemosensors for adenosine triphosphate (ATP) have been reported; however, the conventional designs have problems with their water solubility, selectivity, and sensitivity. Herein, a supramolecular complex of boronic acid-appended γ-cyclodextrin and zinc-dipicolylamine-based pyrene probe (Zn-1/FBγCyD) was designed based on the concept of a “cyclodextrin (CyD)-based supramolecular chemosensor”. As a proof-of-concept, we have demonstrated that this complex exhibits a turn-on fluorescence response to ATP in water at physiological pH with excellent selectivity and sensitivity, owing to the efficient self-assembly of Zn-1/FBγCyD with ATP through synergistic interactions to afford a strongly fluorescent product. Remarkably, Zn-1/FBγCyD demonstrated extremely strong affinity for ATP with the conditional formation constant of (7.71 ± 0.09) × 10⁶ M⁻¹, resulting in the low limit of detection of 18.9 nM. Furthermore, Zn-1/FBγCyD can monitor changes in ATP concentration after the addition of apyrase, hydrolysing ATP to adenosine monophosphate and a phosphate ion. We believe that the presented approach of a CyD-based supramolecular chemosensor will propose a novel design that realises unexplored selectivity in the research field of fluorescent molecular recognition.

The chemotherapeutic Lenvatinib (LVB) and a nitric oxide (NO) photodonor based on a rhodamine antenna (RD-NO) activatable by the highly compatible green light are supramolecularly assembled by a β-cyclodextrin branched polymer (PolyCD). The poorly water-soluble LVB and RD-NO solubilize very well within the polymeric host leading to a ternary supramolecular nanoassembly with a diameter of ~55 nm. The efficiency of the NO photorelease and the typical red fluorescence of RD-NO significantly enhance within the polymer due to its active role in the photochemical and photophysical deactivation pathways. The co-presence of LVB within the same host does not affect either the nature or the efficiency of the photoinduced processes of RD-NO. Besides, irradiation of RD-NO does not lead to the decomposition of LVB, ruling out any intermolecular photoinduced process between the two guests despite sharing the same host. Ad-hoc devised Förster Resonance Energy Transfer experiments demonstrate this to be the result of the not close proximity of the two guests, which are confined in different compartments of the same polymeric host. The supramolecular complex is stable in a culture medium, and its biological activity has been evaluated against HEP-G2 hepatocarcinoma cell lines in the dark and under irradiation with visible green light, using LVB at a concentration well below the IC₅₀. Comparative experiments performed using the polymeric host encapsulating the individual LVB and RD-NO components under the same experimental conditions show that the moderate cell mortality induced by the ternary complex in the dark increases significantly upon irradiation with visible green light, more likely as the result of synergism between the NO photogenerated and the chemotherapeutic.