Dimethylcurcumin and Copper Sulfate-Loaded Silk Nanoparticles for Synergistic Therapy against Breast Cancer

Dimethylcurcumin (ASC-J9) is an organic active pharmaceutical ingredient with anti-inflammatory, antioxidant, and antitumor effects. However, its application has been significantly hindered by poor solubility in aqueous solutions, a short in vivo half-life, low bioavailability after oral administration, and limited accumulation and absorption in target areas. Nano-drug delivery systems can serve as drug carriers to enhance drug delivery, addressing these challenges with improved efficacy and reduced adverse effects. In this study, a microfluidic swirl mixer is used to prepare silk fibroin composite nanoparticles containing ASC-J9 and copper sulfate (CuS), and the effects of different process parameters on silk fibroin nanoparticles (SNPs) were explored and optimized. The synthesized composite ASC-J9-CuS@SNPs exhibited a mean particle diameter of 180 ± 10 nm and PDI of 0.20 ± 0.03. Two-dimensional/three-dimensional (2D/3D) cell experiments showed that the composite nanomaterials have excellent biocompatibility and antitumor activity with a noticeable cancer cell specificity. In vivo experiments showed that ASC-J9-CuS@SNPs effectively controlled tumor growth without causing damage to blood cells and vital organs. Both in vitro and in vivo experiments demonstrated that the anticancer effect was enhanced by photo thermotherapy. The current study provides a promising strategy for using silk fibroin as nanocarriers for breast cancer therapy.