Construction of pH-responsive nanocarriers in combination with ferroptosis and chemotherapy for treatment of hepatocellular carcinoma
作者全名："Yue, Huan; Gou, Luxia; Tang, Zhenrong; Liu, Yuyang; Liu, Shengchun; Tang, Hua"
作者地址："[Yue, Huan; Tang, Hua] Chongqing Med Univ, Inst Viral Hepatitis, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis,Dept Infect Dis,Minis, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China; [Gou, Luxia] Chengdu Fifth Peoples Hosp, Dept Clin Lab, Chengdu 611130, Peoples R China; [Tang, Zhenrong; Liu, Shengchun] Chongqing Med Univ, Dept Endocrine & Breast Surg, Affiliated Hosp 1, Chongqing, Peoples R China; [Liu, Yuyang] Sixth Peoples Hosp Chengdu, Dept Clin Lab, Chengdu, Sichuan, Peoples R China; [Yue, Huan] Zunyi Med Univ, Affiliated Hosp 3, Peoples Hosp Zunyi City 1, Dept Lab Med, Zunyi 563000, Guizhou, Peoples R China"
通信作者："Tang, H (通讯作者)，Chongqing Med Univ, Inst Viral Hepatitis, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis,Dept Infect Dis,Minis, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China.; Liu, SC (通讯作者)，Chongqing Med Univ, Dept Endocrine & Breast Surg, Affiliated Hosp 1, Chongqing, Peoples R China."
关键词：Ferroptosis; Hepatocellular carcinoma; Prussian blue; Sorafenib
摘要："Background: Chemotherapy is widely used to treat hepatocellular carcinoma (HCC). Although sorafenib (SO) is the only chemotherapy drug approved by FDA for treatment of HCC, it is associated with several disadvantages including low water solubility, low bioavailability, lack of targeting and easily causes systemic toxicity. In recent years, nanocarriers have shown promise in drug delivery to effectively solve these problems. Herein, we used SO-loaded nanocarriers to overcome the defects of chemotherapy during treatment of HCC. Specifically, we encapsulated pH-sensitive hollow mesoporous Prussian blue nanoparticles (HMPB) with SO (an inhibitor of multi-kinase and accelerant of ferroptosis) to act as carriers and facilitate drug release. We also coated its surface with a layer of pH-responsive chitosan (CS) to block the drug and increase biocompatibility. Finally, we successfully constructed HP/SO/CS nanocomposites for targeted delivery of chemotherapeutic drugs, with the aim of initiating chemotherapy and ferroptosis for dual treatment of tumors. In vitro and in vivo experiments were performed for evaluation of the nanocomposites' anti-tumor efficacy by using liver cancer cells and mice, respectively. Results: The nanocomposites specifically targeted tumor cells through enhancing permeability and retention (EPR) effect. Results from in vitro experiments showed that the nanocarriers not only promoted cell apoptosis and reduced the number of cells for chemotherapy, but also promoted accumulation of reactive oxygen species (ROSs). In vivo experiments showed that mice in the nanocomposite-treated group exhibited the smallest tumor sizes and body weights, with no obvious damage to normal tissues and organs. Conclusion: Taken together, these findings indicated that nanocarriers had an effective inhibitory effect on HCC cells. This safe and multifunctional treatment model was a valuable option for the treatment of HCC, as well as other cancers."
基金机构："Basic research and frontier exploration project of Yuzhong District of Chongqing ; Key Laboratory of Infectious Diseases, CQMU "
基金资助正文："This study was supported by the Basic research and frontier exploration project of Yuzhong District of Chongqing (20180109), the Key Laboratory of Infectious Diseases, CQMU (202004)."