Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, Marburg, Germany.
Department of Chemistry, Ångstr¨ om Laboratory, Uppsala University, 75237 Uppsala, Sweden.
Eur J Pharm Biopharm. 2024 Nov;204:114503. doi: 10.1016/j.ejpb.2024.114503. Epub 2024 Sep 18.
Since the available treatments are not highly effective to combat cancer, therefore, the alternative strategies are unavoidable. Photodynamic therapy (PDT) is one of the emerging approaches which is target specific and minimally invasive. This study explores the successful development of Poly (D,L-lactide-co-glycolide) (PLGA) coated mesoporous silica nanoparticles (MSNs) and their augmented effects achieved by integrating curcumin (Cur) and cetyltrimethylammonium bromide (CTAB) in the polymeric layer and silica's pores, respectively. The synthesized nanocarriers (Cur-PLGA-cMSNs) have shown preferential targeting to the cellular organelles facilitated by CTAB's and Cur's affinity to mitochondria. CTAB and Cur-based PDT induced oxidative stress and generation of reactive oxygen species (ROS), resulting in dysfunctional mitochondria and triggered apoptotic pathways. PLGA coating has produced multifunctional effects, including; gatekeeping effects at pore openings, providing an extra loading site, enhancing the hemocompatibility of MSNs, and masking the free cur-related prolonged coagulation time. Cur-PLGA-cMSNs, as a multifaceted and combative approach with synergistic effects demonstrate promising potential to enhance outcomes in cancer treatment.
由于现有的治疗方法对于对抗癌症的效果并不高，因此，必须采取替代策略。光动力疗法（PDT）是一种新兴的方法，具有靶向特异性和微创性。本研究探索了聚（D，L-丙交酯-共-乙交酯）（PLGA）包覆介孔硅纳米粒子（MSNs）的成功开发，以及通过分别在聚合物层和硅的孔中整合姜黄素（Cur）和十六烷基三甲基溴化铵（CTAB）来实现其增强效果。合成的纳米载体（Cur-PLGA-cMSNs）显示出对细胞细胞器的优先靶向作用，这得益于 CTAB 和 Cur 对线粒体的亲和力。CTAB 和 Cur 基 PDT 诱导氧化应激和活性氧（ROS）的产生，导致功能失调的线粒体并触发凋亡途径。PLGA 涂层产生了多种功能效应，包括在孔口处的门禁效应、提供额外的负载部位、增强 MSNs 的血液相容性以及掩盖游离的 Cur 相关的延长凝血时间。Cur-PLGA-cMSNs 作为一种具有协同作用的多方面和有战斗力的方法，具有增强癌症治疗效果的巨大潜力。
