pH-responsive tanshinone IIA-loaded hydrogel nanoparticles inducing ferroptosis, autophagy and apoptosis for anticancer treatment

Abstract Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of Salvia miltiorrhiza Bunge (Danshen), a Chinese medicinal herb. However, Tan IIA suffers from low absorption and limited bioavailability due to its poor solubility in water. To address this issue, we utilized calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, enabling enhance the solubility. Besides, the nanoparticles, with pH-responsive property may have great potential on controlled drug delivery. The Tan IIA/CA nanoparticles also exhibited significant anticancer activity in vitro. Furthermore, we investigated the molecular mechanisms underlying the anticancer effect of Tan IIA/CA, revealing the involvement of apoptosis, ferroptosis, and autophagy pathways. This study not only confirms the anticancer properties of Tan IIA/CA, but also provides novel insights and strategies for enhancing the solubility of poorly water-soluble compounds.