Hyaluronic Acid‐Decorated Hollow Nanocapsules for Enhanced Tumor‐Targeted Chemotherapy

The design of innovative drug nanocarriers with high encapsulation efficiency for targeted therapy remains a pivotal focus in biomedical research. Herein, we employed a combination of Friedel–Crafts crosslinking polymerization and N , N ′‐dicyclohexylcarbodiimide/4‐dimethylaminopyridine‐mediated esterification to synthesize hyaluronic acid‐decorated hollow nanocapsules (HA‐HNs) for the active‐targeted delivery of paclitaxel (PTX) to breast cancer cells. HA‐HNs exhibited uniform hollow spheres with a distinctive sea‐urchin‐like morphology, characterized by an average external diameter of ~196 nm. Structural analysis revealed a hierarchical porous architecture featuring abundant micropores and mesopores, with a specific surface area of 558 m 2 /g and a pore size distribution primarily within the 3–5 nm range. The HA‐HNs demonstrated a high drug entrapment efficiency of up to 45.83%. In vitro drug release studies indicated that cumulative PTX release was significantly restricted under neutral pH conditions, whereas accelerated release occurred under acidic conditions, confirming the pH‐responsivity of PTX@HA‐HNs. Moreover, PTX@HA‐HNs exhibited significantly higher cytotoxicity against MCF‐7 cells compared to non‐targeted PTX@HNs, likely due to enhanced cellular internalization mediated by CD44 receptor binding. These results highlight the potential of HA‐HNs as promising nanocarriers for targeted drug delivery in cancer therapy.