Developing novel β‐cyclodextrin‐based nanosponge as nanocarrier of hydroxyurea anticancer agent

Abstract The emergence of advanced nanosponge materials has opened new frontiers in nanotechnology, offering unparalleled structural versatility and surface adaptability. In this study, a novel β‐cyclodextrin (βCD)‐based nanosponge system was synthesized using three distinct cross‐linkers—maleic anhydride, epichlorohydrin, and their combination each—contributing to a unique network architecture with tunable porosity and stability. This study highlights the replacement of toxic cross‐linkers, such as epichlorohydrin with maleic anhydride, offering a more biocompatible alternative. By comparing nanosponge systems synthesized using two crosslinking agents, materials were identified, and the most effective nanomaterial was determined. To further amplify the surface area and functional capacity, halloysite nanotubes (HNT) were incorporated into the system, resulting in an innovative nanocomposite with an expanded, highly accessible interface. Incorporating HNT into the nanosponge matrix significantly enhances the surface area, as evidenced by Brunauer–Emmett–Teller (BET) analysis, which demonstrates a marked increase in both surface area and porosity of the nanosponges. A detailed examination of the synergy between the nanosponge matrix and HNT was conducted through both in situ and ex situ approaches, revealing an intricate interplay that governs the material's integrity and adaptability. Structural characterization through attenuated total reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), proton nuclear magnetic resonance spectroscopy ( 1 H‐NMR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) confirmed the formation of an exceptionally porous, chemically robust nanoscale framework. Significantly, this work underscores the design of a next‐generation, biocompatible nanosponge material, free of toxic components, and featuring an expanded surface area, capable of enhancing the bioavailability of cancer drugs while simultaneously reducing their associated toxicity. This innovative approach opens new avenues for drug delivery systems in cancer therapy and beyond. Highlights β‐cyclodextrin nanosponges were synthesized by MA, EPI, and MA‐EPI. Nanocarrier of β‐cyclodextrin decorated halloysite nanotubes (βCD@HNT) was prepared by a facile route. Nanosponges were applied to the binding and carrying of hydroxyurea (HX@βCD@HNT). Nanosponge and its drug carrier were characterized by FTIR, NMR, XPS, and BET. Morphology of β‐cyclodextrin‐based nanocarriers was enlightened by SEM and TEM.