Delrish Elham, Jabbarvand Mahmoud, Ghassemi Fariba, Asadi Amoli Fahimeh, Atyabi Fatemeh, Heidari Keshel Saeed, Lashay Alireza, Sadat Mirzazadeh Tekie Farnaz, Soleimani Masoud, Dinarvand Rassoul
Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Retina & Vitreous Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
J Ophthalmic Vis Res. 2023 Feb 21;18(1):68-80. doi: 10.18502/jovr.v18i1.12727. eCollection 2023 Jan-Mar.
This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model.
The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration.
NPs had a mean diameter, polydispersity index, and zeta potential of 30 4 nm, 0.24 0.03 and +10 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 2%) and vitreous seeds (89 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection ( = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH ( 0.05).
This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model.
本研究旨在制备含拓扑替康的硫醇化壳聚糖-葡聚糖纳米粒（TPH-CMD-TCS-NPs），以评估纳米粒在兔异种移植模型中提高视网膜母细胞瘤玻璃体内化疗疗效的能力。
采用凝聚法制备纳米粒。使用共聚焦显微镜研究了人视网膜母细胞瘤Y79细胞对菁染料CY3标记纳米粒的细胞摄取。此外，通过四氮唑蓝染料II（XTT）和流式细胞术对制备的TPH-CMD-TCS-NPs进行测试，以评估其细胞毒性。另外，建立了视网膜母细胞瘤兔异种移植模型，通过玻璃体内给药来测试TPH-CMD-TCS-NPs的抗肿瘤效果。
纳米粒的平均直径、多分散指数和zeta电位分别为30±4nm、0.24±0.03和+10±3mV。作为基于剂量的特征，纳米粒（IC50为40.40，而游离拓扑替康为126.20nM；P = 0.022）比游离拓扑替康更有效。通过苏木精和伊红（H&E）染色评估肿瘤组织（91±2%）和玻璃体种子（89±9%）中的坏死百分比，以此来衡量纳米粒玻璃体内化疗的肿瘤反应。与对照组相比，玻璃体内注射7天后，TPH-CMD-TCs-NPs治疗组的肿瘤体积显著减小（P = 0.039）。玻璃体内注射TPH-CMD-TCs-NPs或TPH后，视网膜电图参数未发现显著变化（P>0.05）。
本研究表明，在兔异种移植视网膜母细胞瘤模型中，玻璃体内给药TPH-CMD-TCS-NPs具有明确的抗肿瘤疗效。
