Triple Stimuli Responsive p(NIPAM‐co‐MAA‐co‐SPMA) Hydrogel for Controlled Anticancer Drug Delivery: Synthesis, Characterization, and Performance Evaluation

ABSTRACT A novel triple‐responsive composite hydrogel, p(NIPAM‐co‐MAA‐co‐SPMA), was designed and synthesized via free radical polymerization, incorporating N‐isopropylacrylamide (NIPAM) for temperature responsiveness, methacrylic acid (MAA) for pH sensitivity, and spiropyran methacrylate (SPMA) for light responsiveness. This study aimed to develop a novel stimuli‐responsive sustained release drug delivery system. The composition and structure of the hydrogel were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), X‐ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Doxorubicin (DOX) was used as a model drug to evaluate loading and release behavior. The hydrogel achieved a drug loading content (DLC) of 25.7% and a drug loading efficiency (DLE) of 74.3% and enabled controlled release with approximately 89% cumulative DOX release within 6 h under combined thermal, acidic, and ultra‐violet light stimuli. Cytotoxicity assays and cellular uptake studies confirmed the excellent biocompatibility of the hydrogel and its efficacy in suppressing cancer cell growth. These results highlight the potential of p(NIPAM‐co‐MAA‐co‐SPMA) as an intelligent platform for on‐demand targeted anticancer therapy.