PH/temperature-responsive composite electrospun nanofibers based on chitosan (CS) and N-isopropylacrylamide (NIPAM):...

PH/temperature-sensitive nanofiber drug delivery systems show significant potential in overcoming the clinical limitations of conventional chemotherapy. Key challenges include achieving synergistic dual-sensitivity, balancing nanofiber structural stability with biocompatibility, and integrating efficient drug loading with targeted release. To overcome these challenges, firstly, we regulated the thermal response range and enhanced material hydrophilicity. A thermoresponsive copolymer, poly(N-isopropylacrylamide-co-1-vinylpyrrolidone) [named poly(NIPA-co-VP)], was synthesized via radical solution polymerization. The raw materials for its preparation are NIPA and VP. Subsequently, the pH-sensitive natural biopolymer chitosan was blended with poly(NIPA-co-VP) to prepare a spinning solution. Electrospinning technology was then successfully employed to fabricate novel pH/temperature dual-responsive nanofiber membranes. This membrane combines a high specific surface area (enabling efficient drug loading) with a synergistic dual-sensing response mechanism, adapting to the weakly acidic conditions of the tumor microenvironment and temperature changes induced by local hyperthermia. In vitro drug release experiments using doxorubicin (DOX) as a model drug demonstrated the ability to modulate DOX release kinetics by adjusting external pH and temperature, confirming environmental responsiveness. Observations from laser confocal microscopy, combined with data on cellular uptake and intracellular distribution, indicate that the nanofibers gradually release DOX through responsive regulation. The drug entered cells via active transport mechanisms and ultimately accumulated predominantly in the nucleolar region. This process aligns closely with the mechanism by which DOX exerts its antitumor activity. Additionally, these nanofibers exhibit excellent biocompatibility. The poly(NIPA-co-VP)/CS nanofibers developed in this study achieve efficient dual pH/temperature sensitivity integration via electrospinning. This material demonstrates significant potential for clinical applications.