Department of Ultrasound, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Int J Nanomedicine. 2024 Sep 2;19:8929-8947. doi: 10.2147/IJN.S464178. eCollection 2024.
Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.
Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.
SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.
SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.
细胞死亡调控在癌症治疗领域具有独特的价值。最近，二硫键凋亡引起了广泛的关注。先前的研究报告表明，基于活性氧（ROS）的声动力学疗法（SDT）可以调节癌细胞死亡，从而达到有限的抗癌效果。然而，将 SDT 与二硫键凋亡整合作为一种抗癌策略尚未得到广泛发展。在这项研究中，我们构建了一种人工膜二硫键凋亡声敏剂，即一种同时包裹化疗药物索拉非尼（Sora）和声敏剂氯乙酮 6（Ce6）的纳米脂质体（SC@lip），以实现一站式增强 SDT 效应，诱导二硫键凋亡样癌细胞死亡。
将索拉非尼和 Ce6 共包封到聚乙二醇修饰的脂质体中，通过简单的旋转蒸发声乳化法构建 SC@Lip。评估了 SC@Lip 在超声（US）照射下的细胞吞噬作用、ROS 生成能力、谷胱甘肽（GSH）耗竭能力、脂质过氧化（LPO）和二硫键凋亡样死亡。基于 4T1 皮下肿瘤模型，评估了 SDT 的体内生物安全性和疗效。
SC@Lip 具有高效的细胞吞噬作用。在被 4T1 细胞内吞后，在 SDT 激活下产生大量 ROS，细胞存活率低于 5%。当应用于 4T1 皮下肿瘤模型时，SC@Lip 增强的 SDT 抑制肿瘤生长并延长了小鼠的生存时间。体外和体内实验表明，SC@Lip 可以增强 SDT 效应并触发二硫键凋亡样癌细胞死亡，从而在体外和体内均实现抗肿瘤疗效。
SC@Lip 是一种具有人工膜的多功能纳米平台，可将声敏化和 GSH 耗竭功能集成到一个生物相容的纳米平台中，用于增强 SDT 效应并促进二硫键凋亡样癌细胞死亡。
