electricity, π-π stacking, hydrogen bonding, hydrophobic interaction, metal coordination, and van der Waals forces. Supramolecular chemistry is rooted in life and
medicine. Molecular recognition, the fundamental concept in supramolecular chemistry, is similar to the interaction between enzymes and substrates or more like a
model of “lock and key.” In medicine, the mechanism of drug action is often the
supramolecular interaction between drugs and receptors. Supramolecular medicine
was arised combining supramolecular chemistry with modern medicine, which
emphasis the supramolecular recognition and assembly in medical applications,
promoting the level of modern medicine. Broadly speaking, supramolecular medicine can be defined as the supramolecular agents for the prevention, diagnosis, and
treatment of diseases [1]. The unique and beneficial properties of supramolecular
materials have led to extensive research of their use in the fields of disease diagnosis,
imaging, drug delivery, drug discovery, and precision medicine. Medically, the
emergence of drug-receptor complexes and nanostructure-based drug delivery systems provides new ways to optimize the pharmacokinetic profile of drugs, achieving
more effective treatments with fewer side effects and inactivating toxic substances to
achieve detoxification. This provides new momentum for developing groundbreaking strategies on treatment of cancer and other major diseases [2].
In supramolecular medicine, host-guest interactions are attracting increasing
attention arising from their distinctive properties due to the introduction of macrocyclic hosts into supramolecular systems. Calixarenes, as third-generation macrocyclic molecules, usually have hydrophobic cavities in which the guests can
be embedded. Calixarenes provide ideal platforms for the fabrication of supramolecular medical agents through host-guest molecular recognition. In fact, it can
effectively solve some restrictions that hinder the use of traditional medicine for
clinical applications by taking advantage of host-guest chemistry. For example, the
host-guest complexes can significantly improve the solubility/stability of certain
anticancer drugs under physiological conditions. Supramolecular self-assembly
can facilitate high accumulation of anticancer drugs in tumors, significantly enhance
the therapeutic effect of the anticancer drugs, and reduce their side effects on
normal tissues. Furthermore, functional groups (such as targeting ligands, imaging
agents, or even therapeutic agents) can be readily integrated into the calixarenechemotherapy system, giving these systems multifunctional therapeutic diagnostic
properties. Most importantly, the release of the drug/prodrug loaded in the tumor
can be controlled, as it can be based on the different environments (e.g., pH, redox,
enzyme) presented between the tumor and normal tissue. The dynamic nature of
non-covalent interactions makes supramolecular chemotherapy more versatile than
traditional chemotherapy and nanomedicines that lack stimuli responsiveness.
The aim of the present chapter is to summarize the latest research results from us
and other research groups about calix[n]arenes and their derivatives with respect to
their supramolecular medicine applications in biosensing, bioimaging, gene delivery, drug carriers, and treatment agents, as well as advancing some hints on future
areas of scientific research related to the above topics. We hope that this review will
constitute a useful tool for nonspecialized readers who wish to obtain an overview of
current trends related to calixarenes in supramolecular medicine or for experts who
want to look for a precise entry in a particular application domain.
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J. Gao and D.-S. Guo
medicine. Molecular recognition, the fundamental concept in supramolecular chemistry, is similar to the interaction between enzymes and substrates or more like a
model of “lock and key.” In medicine, the mechanism of drug action is often the
supramolecular interaction between drugs and receptors. Supramolecular medicine
was arised combining supramolecular chemistry with modern medicine, which
emphasis the supramolecular recognition and assembly in medical applications,
promoting the level of modern medicine. Broadly speaking, supramolecular medicine can be defined as the supramolecular agents for the prevention, diagnosis, and
treatment of diseases [1]. The unique and beneficial properties of supramolecular
materials have led to extensive research of their use in the fields of disease diagnosis,
imaging, drug delivery, drug discovery, and precision medicine. Medically, the
emergence of drug-receptor complexes and nanostructure-based drug delivery systems provides new ways to optimize the pharmacokinetic profile of drugs, achieving
more effective treatments with fewer side effects and inactivating toxic substances to
achieve detoxification. This provides new momentum for developing groundbreaking strategies on treatment of cancer and other major diseases [2].
In supramolecular medicine, host-guest interactions are attracting increasing
attention arising from their distinctive properties due to the introduction of macrocyclic hosts into supramolecular systems. Calixarenes, as third-generation macrocyclic molecules, usually have hydrophobic cavities in which the guests can
be embedded. Calixarenes provide ideal platforms for the fabrication of supramolecular medical agents through host-guest molecular recognition. In fact, it can
effectively solve some restrictions that hinder the use of traditional medicine for
clinical applications by taking advantage of host-guest chemistry. For example, the
host-guest complexes can significantly improve the solubility/stability of certain
anticancer drugs under physiological conditions. Supramolecular self-assembly
can facilitate high accumulation of anticancer drugs in tumors, significantly enhance
the therapeutic effect of the anticancer drugs, and reduce their side effects on
normal tissues. Furthermore, functional groups (such as targeting ligands, imaging
agents, or even therapeutic agents) can be readily integrated into the calixarenechemotherapy system, giving these systems multifunctional therapeutic diagnostic
properties. Most importantly, the release of the drug/prodrug loaded in the tumor
can be controlled, as it can be based on the different environments (e.g., pH, redox,
enzyme) presented between the tumor and normal tissue. The dynamic nature of
non-covalent interactions makes supramolecular chemotherapy more versatile than
traditional chemotherapy and nanomedicines that lack stimuli responsiveness.
The aim of the present chapter is to summarize the latest research results from us
and other research groups about calix[n]arenes and their derivatives with respect to
their supramolecular medicine applications in biosensing, bioimaging, gene delivery, drug carriers, and treatment agents, as well as advancing some hints on future
areas of scientific research related to the above topics. We hope that this review will
constitute a useful tool for nonspecialized readers who wish to obtain an overview of
current trends related to calixarenes in supramolecular medicine or for experts who
want to look for a precise entry in a particular application domain.
202
J. Gao and D.-S. Guo