Unimolecular polymer nanomaterials (UPNs) have well-defined structures, desirable stability and designable functional groups, and hence exhibit great application potential in drug delivery. However, the syntheses of UPNs are generally time-consuming and tedious, which greatly limit their applications. In this paper, we present the preparation of a β-cyclodextrin-cored star-shaped polymer with 21 poly(tert-butyl acrylate) arms. This polymer was facilely synthesized by one-step atom transfer radical polymerization (ATRP). After cleaving the tert-butyl ester protecting groups, the abundant carboxylic acid side groups were used to incorporate doxorubicin (DOX), phenylboronic acid (PBA) groups and poly(ethylene glycol) (PEG) to achieve drug loading and tumor drug delivery. Due to the tumor-targeting ability of the PBA groups, this UPN-based nanomedicine showed high tumor accumulation, penetration and therapeutic efficacy.