Preparation of pH-Responsive Tanshinone IIA-Loaded Calcium Alginate Nanoparticles and Their Anticancer Mechanisms
Tianying Ren,
Jing Wang,
Yingxin Ma,
Yichen Huang,
Somy Yoon,
Lijun Mu,
Ru Li,
Xuekun Wang,
Lina Zhang,
Pan Li,
Lusha Ji
Affiliations
Tianying Ren
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, College of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China
Jing Wang
Key Laboratory for Pediatrics of Integrated Traditional and Western Medicine, Liaocheng People’s Hospital, Liaocheng 252000, China
Yingxin Ma
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Yichen Huang
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Somy Yoon
College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea
Lijun Mu
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Ru Li
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Xuekun Wang
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Lina Zhang
College of Medicine, Liaocheng Vocational and Technical College, Liaocheng 252000, China
Pan Li
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China
Lusha Ji
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, College of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China
Background: Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of Salvia miltiorrhiza Bunge (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. Methods: 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. Results: 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. Conclusions: 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.
