Recent Developments of Supramolecular Metal-based Structures for Applications in Cancer Therapy and Imaging

Abstract

The biomedical application of discrete supramolecular metal-based structures, including supramolecular coordination complexes (SCCs), is still an emergent field of study. However, pioneering studies over the last 10 years demonstrated the potential of these supramolecular compounds as novel anticancer drugs, endowed with different mechanisms of action compared to classical small-molecules, often related to their peculiar molecular recognition properties. In addition, the robustness and modular composition of supramolecular metal-based structures allows for an incorporation of different functionalities in the same system to enable imaging in cells via different modalities, but also active tumor targeting and stimuli-responsiveness. Although most of the studies reported so far exploit these systems for therapy, supramolecular metal-based structures may also constitute ideal scaffolds to develop multimodal theranostic agents. Of note, the host-guest chemistry of 3D self-assembled supramolecular structures - within the metallacages family - can also be exploited to design novel drug delivery systems for anticancer chemotherapeutics. In this review, we aim at summarizing the pivotal concepts in this fascinating research area, starting with the main design principles and illustrating representative examples while providing a critical discussion of the state-of-the-art. A section is also included on supramolecular organometallic complexes (SOCs) whereby the (organic) linker is forming the organometallic bond to the metal node, whose biological applications are still to be explored. Certainly, the myriad of possible supramolecular metal-based structures and their almost limitless modularity and tunability suggests that the biomedical applications of such complex chemical entities will continue along this already promising path.

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

“…Transition metal complexes are particularly suited to controlled drug release, having bonds that are highly responsive to their environment [121]. Such cases are applied when prodrug complexes can be designed that are inert under normal physiological conditions, but become labile with a change in environment such as redox status, pH, or the localized application of light [126][127][128]. By not activating a drug before it reaches its target, side reactions and premature metabolism that can lead to undesirable side effects to normal cells can be reduced tremendously [110][111][112][113][114][115][116]127,129].…”

Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts

“…The binding of CD and CdTe/ZnS QDs was confirmed by 1 H NMR spectrum ( Figure S1 ). CD and ADA complexes have been used in various supramolecular systems for biomedical applications 32 , 33 . Therefore, ADA-PEG-TCP1 was designed to incorporate the targeting probe into the CD-QD surface.…”

Dimensional Matching versus Induced‐Fit Distortions: Binding Affinities of Planar and Curved Polyaromatic Hydrocarbons with a Tetragold Metallorectangle

“…During the last three years, we started introducing the use of rigid poly‐N‐heterocyclic carbene ligands for the preparation of new metallosupramolecular entities. This type of supramolecular organometallic compounds (SOCs), in which the linker ligand establishes organometallic bonds to the metal, have been rarely studied as host compounds. In particular, we recently reported a series of supramolecular coordination compounds based on a pyrene‐bis‐imidazolylidene ligand .…”