Design of Temperature-Sensitive Hydrogel Nanoparticles and Investigation of Their Application in the Development of a New Generation of Anti-Cancer Drugs with Optimization Conditions by Central Composite Design

Temperature-sensitive nanohydrogels present notable advantages in biomedical applications due to their high permeability, selectivity, water solubility, and minimal invasiveness, making them ideal carriers for controlled chemotherapy drug delivery. In this study, a novel polyphenylglycine-based nanohydrogel was synthesized via N-phenylglycine polymerization and subsequently functionalized with heat-responsive and allylamine groups to improve solubility and introduce additional active sites. The multi-target anticancer drug, sunitinib malate (Sun), was then incorporated into the nanohydrogel for targeted delivery. The structure of the nanohydrogel was confirmed via FTIR, XRD, FE-SEM, EDX, and TGA analyses. Drug loading parameters, including pH, contact time, and temperature, were optimized using response surface methodology, yielding optimal conditions at pH 7.4, 60 minutes, and 50 °C. Adsorption followed the Langmuir isotherm (19.81 mg/g monolayer capacity), and the kinetics were best described by a pseudosecond-order model. The nanohydrogel exhibits a lower critical solution temperature slightly above physiological temperature and demonstrates excellent photothermal stability. These properties highlight its potential as a promising platform for controlled and targeted delivery of anti-cancer therapeutics.