溶瘤病毒和化疗方式的共同递送:长春新碱对抗前列腺癌治疗:一种有效的病毒化疗方法。
Co-delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro-chemotherapeutic approach.
发表日期:2024 Jul
作者:
Sadia Anjum, Faiza Naseer, Tahir Ahmad, Afrose Liaquat, Maisa S Abduh, Kousain Kousar
来源:
JOURNAL OF MEDICAL VIROLOGY
摘要:
前列腺癌是男性中常见的癌症,传统的治疗选择通常很有限。细胞毒性化疗尽管有其缺点,但仍然是主流。我们提出了一种针对溶瘤麻疹病毒(OMV)和长春新碱(VC)的纳米级递送单元的靶向联合递送方法,以提高治疗效果。 HA 包被的 OMV VC 负载 TC 纳米制剂专为前列腺癌的靶向溶瘤活性而设计。前列腺癌细胞系中的 CD44 表达分析表明 PC3 细胞中的表达显着高。使用专家设计 (DOE) 进行纳米制剂的优化,详细描述了 HA 包覆的 OMV VC 负载 TC 纳米制剂的制备和表征,显示平均粒径为 397.2±0.01nm,多分散指数为 0.122,zeta 电位为 19.7 0.01mV。结果表明,成功的封装效率为 2.4 × 106 TCID50/Ml,并且 OMV 和 VC 从纳米制剂中持续释放长达 72 小时。体外试验表明,PC3 细胞的细胞活力为 10±0.71%,HPrEC 的细胞活力为 73±0.66%,具有有效的抗癌活性,90μg/ml 剂量和时间依赖性的形态学变化显着。复合制剂在 PBS 中的浓度为 50μg PI/ml 时显示阳性细胞死亡率为 49.5±0.02%,细胞周期停滞在 G2/M 期 54.3%,G0/G1 期 8.1%,S 期 5.7%,并具有显着的线粒体膜电位(MMP) 为 50μg/ml,通过流式细胞术 (FACS) 评估。表面整合配体方法增强了溶瘤病毒和化疗药物的靶向递送,为前列腺癌治疗提供了潜在的替代方案,并表明在纳米制剂中共同施用 VC 和 OMV 可以改善治疗结果,同时减少化疗药物剂量。© 2024威利期刊有限责任公司。
Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.© 2024 Wiley Periodicals LLC.