Biomedical Applications of Calixarenes: State of the Art and Perspectives

Abstract

Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited structure and application possibilities due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various noncovalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self‐assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in vitro diagnosis (biosensing), in vivo diagnosis (bioimaging), and therapy.

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

“…Certain AIE-active therapeutic nanoplatforms can be constructed by modifying their structures with amphiphilic moieties. For example, a nonviral gene vector can be constructed by the self-assembly of [12]aneN 3 and triphenylamine-benzylideneimidazolone exhibiting the AIE effect, condensation of DNA, and improvement of their transfection in the presence of DOPE (the helper for DNA condensation and transfection). [52] The triphenylamine unit is hydrophobic, while the macrocyclic polyamine [12]aneN 3 unit is hydrophilic possessing the ability of DNA condensation.…”

“…For example, a nonviral gene vector can be constructed by the self-assembly of [12]aneN 3 and triphenylamine-benzylideneimidazolone exhibiting the AIE effect, condensation of DNA, and improvement of their transfection in the presence of DOPE (the helper for DNA condensation and transfection). [52] The triphenylamine unit is hydrophobic, while the macrocyclic polyamine [12]aneN 3 unit is hydrophilic possessing the ability of DNA condensation. Thus, this AIE-active gene vector combined multiple functions and characteristics, such as two-photon fluorescent tracking of DNA, pH/enzyme responsiveness, and improved DNA transfection.…”

“…The structures benefit from ordered architectures, tailored morphologies, controllable functions, and enhanced permeability and retention (EPR) effect. [12] Certain diagnostic modalities such as fluorescence imaging (FLI), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) are commonly integrated into supramolecular theranostics to achieve effective and precise treatment of complex diseases [13] Among such imaging technologies, FLI has attracted significant scientific interest due to its highly sensitive, rapidly responsive, and non-invasive features. [14] However, conventional organic fluorophores typically exhibit notorious aggregation-caused quenching (ACQ) in the aggregated state.…”

Topical Delivery of Curcumin by Choline-Calix[4]arene-Based Nanohydrogel Improves Its Therapeutic Effect on a Psoriasis Mouse Model

“…In the search for novel building blocks to realize nanostructured drug delivery systems, calix[n]arene macrocycles are attractive molecular scaffolds [ 11 , 12 ]. The calix[n]arene skeleton can be variously functionalized to give amphiphilic derivatives capable to assemble in micelles, vesicles, solid lipidic nanoparticles, and gels [ 13 ] of interest for biomedical and pharmaceutical applications [ 15 ].…”

Supramolecular design based activatable magnetic resonance imaging

“…12 A variety of complex functional supramolecular structures have been produced through the self-assembly process. 13 Supramolecular chemistry has been widely used in biomedical fields, as it utilizes the reversible and dynamic nature of noncovalent forces, 14 to construct a series of activatable events, such as activatable fluorescence imaging, 15 activatable photodynamic therapy, 16 activatable chemotherapy (supramolecular chemotherapy), 17 and activatable theranostics. 18 Similarly, supramolecular chemistry has also been used to perform activatable MRI, where an MRI contrast agent forms aggregates or host-guest complexes, accompanied by a change in the relaxation time due to slower tumbling.…”