Cheng Qianqian, Liu Guangxuan, Yin Xiaojing
Department of Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, and Institute, Shenyang-110042, China.
Heliyon. 2023 Jul 19;9(9):e18413. doi: 10.1016/j.heliyon.2023.e18413. eCollection 2023 Sep.
To develop innovative drug delivery carriers for controllable release and cancer-targeted delivery of therapeutic agents to accomplish efficient cancer chemotherapy. Herein we effectively fabricated CaCO primarily loaded biotin (BT) and directly the self-assembly of oxaliplatin (Pt (IV)) prodrugs form in liposomes. The acquired BT-Pt (IV)@PEG/CaCO with outstanding biological stability displays rapid pH-mediated degradations, thus allowing the effective pH-responsive delivery of BT. In vitro, anticancer assays proved that BT-Pt (IV)@PEG/CaCO effectively kills the thyroid cancer cells (B-CPAP and FTC-133). The biochemical staining assays investigated the morphological changes of thyroid cancer after treatment with nanoparticles. The DNA fragmentation of the cells was assessed by utilizing the comet assay. BT-Pt (IV)@PEG/CaCO increased ROS levels and caused mitochondrial membrane potential and DNA damage, which resulted in apoptosis. Due to its versatile drug-loading capability, this research demonstrates that CaCO liposomal formulation is a biocompatible and reliable substrate for establishing pH-mediated drug delivery methods and promising for possible therapeutic application.
为开发用于治疗剂可控释放和癌症靶向递送的创新药物递送载体,以实现高效的癌症化疗。在此,我们有效地制备了主要负载生物素(BT)的碳酸钙,并直接在脂质体中形成奥沙利铂(Pt(IV))前药的自组装体。所获得的具有出色生物稳定性的BT-Pt(IV)@PEG/CaCO显示出快速的pH介导降解,从而实现BT的有效pH响应递送。在体外,抗癌试验证明BT-Pt(IV)@PEG/CaCO能有效杀死甲状腺癌细胞(B-CPAP和FTC-133)。生化染色试验研究了纳米颗粒处理后甲状腺癌的形态变化。利用彗星试验评估细胞的DNA片段化。BT-Pt(IV)@PEG/CaCO增加了活性氧水平并导致线粒体膜电位和DNA损伤,从而导致细胞凋亡。由于其具有多功能的载药能力,本研究表明碳酸钙脂质体制剂是建立pH介导药物递送方法的生物相容性和可靠基质,有望用于可能的治疗应用。