Abstract
Abstract Doxorubicin (DOX) has been used in the treatment of various malignant tumors, including cervical cancer. However, the application of DOX is seriously hampered by the side effects, especially the cardiotoxicity, hepatotoxicity and nephrotoxicity. Sodium new houttuyfonate (SNH), a structurally modified derivative of Houttuynia cordata Thunb., possesses anti-tumor and anti-inflammatory activity. This study designed an SNH and DOX co-loaded liposome (SNH@DOX Lipos) to deliver the two drugs within tumor cells and reduce DOX induced systemic toxicity. The results indicated that SNH@DOX Lipos had an average size of 136.1 ± 2.24 nm with a PDI of 0.236 ± 0.03. The encapsulation efficiency of either SNH or DOX was more than 80%. Further study clarified that preferential release of SNH@DOX Lipos contributed to facilitating greater accumulation of drugs within the tumors. The combination of free SNH and DOX exerted a synergistic anti-cervical cancer effect. Moreover, SNH@DOX Lipos enhanced anti-cervical cancer efficacy and induced cell apoptosis via the TNF-α/RIP1/NF-κB signaling pathway. Also, SNH@DOX Lipos decreased the secretion of IL-6 and TNF-α in heart tissue and the serum ALT, AST and BUN levels, reducing systemic toxicity caused by DOX. Therefore, SNH@DOX Lipos may have promising prospects for the treatment of cervical cancer.