pH-sensitive Silk Fibroin Nanoparticles Encapsulating Β-Hydroxyisovalerylshikonin for Targeted Pancreatic Cancer Therapy

Abstract

Background: Pancreatic cancer is a highly malignant tumor with a poor prognosis, and current treatment methods have limited effectiveness. Therefore, developing new and more effective therapeutic strategies is crucial. This study aims to establish pH-responsive silk fibroin (SF) nanoparticles encapsulating β-hydroxyisovalerylshikonin (SF@β-HIVS) to enhance the therapeutic effects against pancreatic cancer.

Methods: SF@β-HIVS nanoparticles were prepared using a self-assembly technique and characterized under different pH conditions using scanning electron microscopy (SEM) and dynamic light scattering (DLS). The effects of SF@β-HIVS on the viability, apoptosis, and migration of PANC-1 cells were assessed through in vitro experiments. Additionally, in vivo experiments using a PANC-1 xenograft mouse model evaluated the antitumor activity and biosafety of SF@β-HIVS.

Results: SF@β-HIVS nanoparticles exhibited a uniformly distributed spherical structure under pH 7.4 conditions and rapidly disintegrated in acidic environments, releasing the drug. In vitro experiments demonstrated that SF@β-HIVS significantly inhibited PANC-1 cell proliferation, induced apoptosis, and suppressed cell migration. In vivo, experiments confirmed the significant antitumor activity and good biosafety of SF@β-HIVS.

Conclusion: This study successfully developed pH-responsive SF@β-HIVS nanoparticles and validated their potential in treating pancreatic cancer. These findings provided a foundation for the clinical application of SF@β-HIVS in pancreatic cancer treatment.

Keywords: Drug delivery.; Pancreatic cancer; Silk fibroin; nanoparticles; pH-responsive; β-hydroxyisovalerylshikonin.