Amplification of oxidative stress with lycorine and gold-based nanocomposites for synergistic cascade cancer therapy

Journal of Nanobiotechnology

Zezhu Zhou¹  Zihui Liang¹  Qingcheng Song²  Xin Xing²  Shangyu Wang³  Wenbo Yang³  Binglong Zhong³  Zengwu Shao³  Baichuan Wang³  Yingze Zhang⁴  Hongzhi Hu⁴  Weijian Liu⁴  Jian Zhu⁵  Xiangtian Deng⁵ 

[1] Collaborative Innovation Center for Advanced Organic Chemical Materials Co-Constructed By the Province and Ministry, Hubei University, 430062, Wuhan, China;Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, 050051, Shijazhuang, China;Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, 050051, Shijazhuang, China;School of Medicine, Nankai University, 300071, Tianjin, China;

关键词: Oxidative stress;    Mitochondrial dysfunction;    Endoplasmic reticulum stress;    Osteosarcoma;    Lycorine;    Gold nanostars;    Mesoporous silica;   

DOI  :  10.1186/s12951-021-00933-1

来源: Springer

【 摘 要 】

BackgroundDespite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy.Methods and resultsA novel nanocomposite, composed of folic acid (FA) modified mesoporous silica–coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice.ConclusionAll these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.

【 授权许可】

CC BY