Active-targeting pH/temperature-responsive magnetic nanocarriers based on poly(N-isopropylacrylamide) and spermine-dendronized magnetite nanoparticles for controlled cyclophosphamide delivery

A novel active-targeting pH/temperature-responsive magnetic nanocarrier (ATM) was developed by conjugating carboxylic acid-terminated poly(N-isopropylacrylamide) with spermine-dendronized magnetite nanoparticles. Cyclophosphamide (CP) was loaded onto ATM through a batch adsorption process, which was optimized utilizing a Box-Behnken design. Optimal conditions (pH 7.5, 30 degrees C, 0.05 g ATM) achieved a 262.47 mg/g loading capacity. The thermodynamic parameters (Delta G, Delta H, and Delta S) confirmed that the adsorption process was spontaneous and exothermic. The Langmuir and Temkin isotherms demonstrated a monolayer physical interaction between CP and ATM. The drug release behavior of CP from ATM was evaluated at pH levels of 7.4 (healthy tissues) and 5.3 (tumor environments), at temperatures above and below the lower critical solution temperature (40 degrees C). At pH 7.4 and 37 degrees C, drug release was minimal (3.64 %), but significantly increased (84%) at pH 5.3 and 45 degrees C. This pH/temperature-sensitive release profile was better fitted to the Korsmeyer-Peppas kinetic model, indicating a Fickian diffusion behavior. ATM-CP exhibited effective uptake by PC3 prostate cancer cells via the polyamine transport system, demonstrating its tumor-targeting potential. This active targeting and controlled drug release in cancer cells suggests that ATM may potentially reduce systemic toxicity while enhancing the efficacy of chemotherapy.