Calixarene-integrated nano-drug delivery system for tumor-targeted delivery and tracking of anti-cancer drugs in vivo

Nano-drug delivery systems (nanoDDS) have been extensively investigated clinically to improve the therapeutic effect of anti-cancer drugs. However, the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application. In this work, a calixarene-integrated nanoDDS (CanD) that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented. The hypoxia-responsive calixarene (SAC4A) exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B (RhB) under normoxic condition while decreasing the binding affinity under hypoxic condition, which leads to the drug release and fluorescence recovery simultaneously. Furthermore, the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability, resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice. Moreover, CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-guest interaction with SAC4A.