A Novel Cobalt‐Based Molecular Container for pH‐Responsive Delivery and Synergistic Enhancement of Sorafenib Antitumor Efficacy

ABSTRACT Sorafenib (SOR) has fast‐track review status due to its dual tumor‐inhibitory mechanism, but its clinical use is limited by severe side effects. This study aimed to develop a new nanocarrier to encapsulate SOR, leveraging the rise of nanomaterials in drug delivery. A coordination molecular container (CoTPE) was synthesized through the self‐assembly of 4′‐(1,2,2‐triphenylvinyl)‐[1,1′‐biphenyl]‐3,5‐dicarboxylic acid as a bridging ligand with Co(II) and sulfonyl‐bridged calix[4]arene. The resultant structure, comprising a cylindrical internal cavity and four bowl‐like external cavities, was characterized by single‐crystal X‐ray diffraction. Spectroscopic titration further validated the ability of the molecular container to encapsulate SOR, exhibiting pH‐sensitive, controlled‐release behavior. Subsequent in vitro and in vivo assessments revealed that CoTPE displayed favorable biocompatibility and enhanced tumor‐suppressing efficacy relative to free SOR. This study not only introduces a promising strategy for the targeted delivery of SOR in liver cancer therapy but also expands the utility of innovative supramolecular materials and molecular containers in biomedical and pharmaceutical applications.