“…The design of drug delivery systems (DDSs) is an important part of molecular engineering that demonstrates the use of formulation strategies to evade side effects of drugs, improve their therapeutic effects, and endow more functions to drugs . Conventionally, DDSs have been rationally fabricated based on polymers, − liposomes, − proteins, , and inorganic nanoparticles. − The drugs loaded in the conventional DDSs are commonly linked by covalent bonds, coordination interactions, hydrophobic interactions, and so on. − In addition, polyethylene glycol (PEG) is commonly introduced into DDSs to improve the water solubility and prolong the circulation of drugs. − However, the stability along the circulation process and controlled release of loaded drugs in the tumor environment are not easily compatible in conventional DDSs. The host–guest interaction is a kind of well-established noncovalent interaction that takes advantages of its wide-range binding affinity and stimuli-responsive properties. − By combination of host–guest interaction and DDSs, the stability of loaded drugs can be improved and their cytotoxicity can be inhibited owing to the encapsulation by strong host–guest interactions. − Meanwhile, controlled release of the drugs can be achieved through the specific response of the host–guest interaction to the overexpressed biomarkers in the tumor microenvironment, leading to the recovery of the antitumor bioactivities of drugs. − However, host–guest interaction in DDSs may be affected under the physiological environment because of the complex components in the environment.…”