Wang Yubo, Zhou Yong, Wang Jinling, Zhang Lu, Liu Chen, Guo Ding, Yu Yanlin, Ye Roumei, Wang Yun, Xu Bing, Luo Yiming, Chen Dengyue
Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen 361003 China.
Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen 361003 China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350108, China.
Int J Pharm. 2025 Feb 25;671:125294. doi: 10.1016/j.ijpharm.2025.125294. Epub 2025 Jan 28.
The limited selectivity and high systemic toxicity of traditional chemotherapy hinder its efficacy in treating diffuse large B-cell lymphoma (DLBCL). The combination of sonodynamic therapy (SDT) with chemotherapy has emerged as a novel strategy for cancer treatment, aiming to improve therapeutic outcomes and reduce systemic toxicity. However, challenges such as elevated drug clearance rates and non-selecitivity remain to be resolved. This study has developed a biocompatible nanomedicine delivery system, PA-HM@DOX/ICG, employing hollow mesoporous silica nanoparticles (HMSNs) as the nanocarrier. The nanomedicine incorporates the chemotherapeutic agent doxorubicin (DOX) along with the sonosensitizer indocyanine green (ICG) within its encapsulation, and undergoes additional surface modification using lipid-nucleic acid conjugates (DSPE-PEG-AS1411) to facilitate active targeted delivery. In vitro cellular experiments have validated that PA-HM@DOX/ICG can specifically recognize and be internalized by SU-DHL-4 lymphoma cells due to the overexpression of nucleolin on their surface. The synergistic effects of DOX-induced DNA damage and reactive oxygen species (ROS) generated by ultrasound-activated ICG induce apoptosis in these cells. Furthermore, PA-HM@DOX/ICG displays minimal toxicity towards LO2 normal hepatocytes, indicating a favorable biosafety profile. In vivo animal studies have shown that PA-HM@DOX/ICG effectively accumulates in tumor sites in mice through both the enhanced permeability and retention (EPR) effect and nucleolin-mediated targeting. Under ultrasound irradiation, PA-HM@DOX/ICG significantly inhibits tumor growth. This study introduces a nanoplatform that integrates chemotherapy with sonodynamic therapy, offering a novel approach for the efficient treatment of DLBCL.
传统化疗的选择性有限且全身毒性高，这限制了其在治疗弥漫性大B细胞淋巴瘤（DLBCL）中的疗效。声动力疗法（SDT）与化疗相结合已成为一种新型癌症治疗策略，旨在提高治疗效果并降低全身毒性。然而，诸如药物清除率升高和非选择性等挑战仍有待解决。本研究开发了一种生物相容性纳米药物递送系统PA-HM@DOX/ICG，采用中空介孔二氧化硅纳米颗粒（HMSNs）作为纳米载体。该纳米药物在其封装内包含化疗药物阿霉素（DOX）以及声敏剂吲哚菁绿（ICG），并使用脂质-核酸缀合物（DSPE-PEG-AS1411）进行额外的表面修饰，以促进主动靶向递送。体外细胞实验证实，由于SU-DHL-4淋巴瘤细胞表面核仁素的过表达，PA-HM@DOX/ICG可以特异性识别并被其内化。DOX诱导的DNA损伤与超声激活的ICG产生的活性氧（ROS）的协同作用诱导这些细胞凋亡。此外，PA-HM@DOX/ICG对LO2正常肝细胞的毒性极小，表明其具有良好的生物安全性。体内动物研究表明，PA-HM@DOX/ICG通过增强的渗透和滞留（EPR）效应以及核仁素介导的靶向作用有效地在小鼠肿瘤部位蓄积。在超声照射下，PA-HM@DOX/ICG显著抑制肿瘤生长。本研究介绍了一种将化疗与声动力疗法相结合的纳米平台，为DLBCL的有效治疗提供了一种新方法。
