Benedetto Gregory, Fowler Anthony, Langdon Dan, Raine Maya, White Molly Lynne, Ogle Joshua, Garmon Corey, Ogle Craig, Richardson Christine
Center for Biomedical Engineering and Sciences, University of North Carolina at Charlotte, 9201 University Blvd., Charlotte, NC 28223, USA.
Biomolecules. 2025 Aug 4;15(8):1123. doi: 10.3390/biom15081123.
Ovarian cancer is a deadly gynecological malignancy that will affect about 21,000 women and result in almost 153,000 deaths in the United States in 2025. New clinical tools that facilitate early diagnosis and treatment of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. We utilized a previously identified single-strand DNA aptamer RLA01 that binds and internalizes into target epithelial ovarian cancer cells to label PLGA-based nanoparticles and determine their ability to selectively target EOC cells and deliver payloads for cellular internalization. Nanoparticles labeled with RLA01 significantly enhanced cellular uptake 20-85% by receptor-mediated endocytosis into target EOC Caov-3 cells and inhibited cellular uptake in non-target HOSE 6-3 cells. Further, labeling of paclitaxel-loaded nanoparticles with RLA01 significantly decreased cell proliferation and induced apoptosis. A preliminary pilot study looking at the in vivo stability of aptamers demonstrated their ability to promote retention and honing of nanoparticles at tumors. These data demonstrate the effective combinatorial use of aptamer RLA01 and nanoparticle technologies for the direct targeting of tumor cell populations both in vitro and in vivo.
卵巢癌是一种致命的妇科恶性肿瘤，2025年在美国将影响约2.1万名女性，并导致近15.3万人死亡。有助于卵巢恶性肿瘤早期诊断和治疗的新型临床工具将显著有助于降低死亡率并提高当前的长期生存率。我们利用先前鉴定的单链DNA适配体RLA01，其可结合并内化到靶上皮性卵巢癌细胞中，以标记基于聚乳酸-羟基乙酸共聚物（PLGA）的纳米颗粒，并确定其选择性靶向卵巢上皮性癌（EOC）细胞并递送有效载荷以实现细胞内化的能力。用RLA01标记的纳米颗粒通过受体介导的内吞作用，使靶EOC Caov-3细胞的细胞摄取显著增强20%-85%，并抑制非靶HOSE 6-3细胞的细胞摄取。此外，用RLA01标记载有紫杉醇的纳米颗粒可显著降低细胞增殖并诱导凋亡。一项关于适配体体内稳定性的初步试点研究表明，它们能够促进纳米颗粒在肿瘤部位的滞留和聚集。这些数据证明了适配体RLA01与纳米颗粒技术的有效组合应用，可在体外和体内直接靶向肿瘤细胞群体。
