Covalently self-assembled polymer nanocapsules based on cucurbit[6]uril have been previously prepared and their applications in payload delivery and bioimaging have been demonstrated, showing significant potentials.1 However, the preparation of these nanocapsules often required time-consuming and laborious multi-step processes, including a low-yield conversion of perhydroxycucurbit[6]uril to perallyloxycucurbit[6]uril, subsequent photopolymerization of perallyloxycucurbit[6]uril with dithiol linkers, and two additional steps of treatment to remove disulfide loops and to create cationic sulfonium respectively.2 Herein we report a novel, facile approach leading to cucurbit[6]uril-based polymer nanocapsules (NCs) via direct alkylation of perhydroxycucurbit[6]uril with a ditopic linker (Scheme 1), thereby saving significant time and efforts, which may lead to significant expansion in investigations of these unique materials in various applications, particularly biomedical sciences.3 In particular, 4,4'-bis(bromomethyl)azobenzene (BBA) may lead to CB[6] NCs responsive to hypoxic conditions that are specific to cancer tissues and cells. We further demonstrated that chemotherapeutic agents such as doxorubicin hydrochloride (DOX·HCl) or photodynamic agents such as Chlorin e6 may get encapsulated inside the nanocapsules, and improved, targeted therapy against cancer cells were observed. This study provided the most facile method leading to NCs that may exhibit stimuli-responsive behaviors for targeted cancer therapy.