Development of calixarene-based drug nanocarriers

Chemotherapy is widely used for cancer treatment. However, many chemotherapeutic drugs are insoluble in water, and many show similar toxicities toward target cells and healthy cells. Hence, the research and development of drug carriers have attracted considerable attention. Calixarenes are a class of macrocyclic substances with excellent drug carrier properties including low cytotoxicity and no hemolytic activity. Calixarenes are easily functionalized at various sites on the upper and lower rims. Following modulation with the appropriate groups, calixarenes self-assemble or assemble with guest molecules into various nanostructures. In addition, calixarenes can form composite nanomaterials with metals and nonmetals. Drugs can be loaded into calixarene-based associates by solubilization/encapsulation, host-guest reactions, and adsorption. These calixarene-based associates provide multiple loading sites for drugs, including the macrocyclic cavity, micellar interior, and internal nanopore and nanocage. Thus, multi-drug delivery strategies can be developed. Furthermore, calixarene-based associates are also convenient to prepare; their structures are easy to adjust, and they can respond to external stimuli. This facilitates a sustained release of drugs, thus reducing drug side effects and improving drug efficacy. Additionally, because of the antibacterial/anticancer activities of metal/metal oxides, their introduction into the calixarene-based drug carrier platform further improves the therapeutic effect of drugs. These developments have opened up a broad prospect for the application of calixarene-based drug delivery platforms in tumor therapy. In this review, we summarize recent research progress for calixarene-based drug carriers, focusing on the construction of associates and drug loading and release performance. The challenges and prospects for future developments are also provided in this review.