Preparation of pH-Responsive Tanshinone IIA-Loaded Calcium Alginate Nanoparticles and Their Anticancer Mechanisms.

Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. : To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility. We also prepared nanoparticles with pH-responsive properties to explore their potential for controlled drug delivery. The physicochemical properties of Tan IIA/CA nanoparticles were evaluated, including their size, stability, and release profile. We also utilized RNA sequencing to further investigate the underlying anticancer mechanisms of Tan IIA/CA nanoparticles. : The Tan IIA/CA nanoparticles demonstrated enhanced solubility and exhibited potent anticancer activity in vitro. Additionally, the nanoparticles showed promising pH-responsive behavior, which is beneficial for controlled release applications. Further investigation into the molecular mechanisms revealed that the anticancer effects of Tan IIA/CA were mediated through apoptosis, ferroptosis, and autophagy pathways. This study confirms the anticancer potential and mechanisms of Tan IIA, while also presenting an innovative approach to enhance the solubility of this poorly soluble compound. The use of CA-based nanoparticles could be a valuable strategy for improving the therapeutic efficacy of Tan IIA in cancer treatment.