Assi Sara, Hayar Berthe, Pisano Claudio, Darwiche Nadine, Saad Walid
Biomedical Engineering Program, American University of Beirut, Beirut 1107 2020, Lebanon.
Department of Biochemistry & Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon.
Nanomaterials (Basel). 2024 Aug 23;14(17):1380. doi: 10.3390/nano14171380.
Cancer is a major public health problem that ranks as the second leading cause of death. Anti-cancer drug development presents with various hurdles faced throughout the process. Nanoparticle (NP) formulations have emerged as a promising strategy for enhancing drug delivery efficiency, improving stability, and reducing drug toxicity. Previous studies have shown that the adamantyl retinoid ST1926 displays potent anti-tumor activities in several types of tumors, particularly in colorectal cancer (CRC). However, phase I clinical trials in cancer patients using ST1926 are halted due to its low bioavailability. In this manuscript, we developed ST1926-NPs using flash nanoprecipitation with polystyrene-b-poly (ethyleneoxide) as an amphiphilic stabilizer and cholesterol as a co-stabilizer. Dynamic light scattering revealed that the resulting ST1926-NPs Contin diameter was 97 nm, with a polydispersity index of 0.206. Using cell viability, cell cycle analysis, and cell death assays, we showed that ST1926-NP exhibited potent anti-tumor activities in human CRC HCT116 cells. In a CRC xenograft model, mice treated with ST1926-NP exhibited significantly lowered tumor volumes compared to controls at low drug concentrations and enhanced the delivery of ST1926 to the tumors. These findings highlight the potential of ST1926-NPs in attenuating CRC tumor growth, facilitating its further development in clinical settings.
癌症是一个重大的公共卫生问题，是第二大死因。抗癌药物研发过程面临各种障碍。纳米颗粒（NP）制剂已成为一种有前景的策略，可提高药物递送效率、改善稳定性并降低药物毒性。先前的研究表明，金刚烷基视黄酸ST1926在几种类型的肿瘤中，特别是在结直肠癌（CRC）中显示出强大的抗肿瘤活性。然而，由于其低生物利用度，使用ST1926的癌症患者一期临床试验已暂停。在本手稿中，我们使用快速纳米沉淀法，以聚苯乙烯-b-聚（环氧乙烷）作为两亲性稳定剂，胆固醇作为共稳定剂，制备了ST1926-NP。动态光散射显示，所得ST1926-NP的平均直径为97nm，多分散指数为0.206。通过细胞活力、细胞周期分析和细胞死亡检测，我们表明ST1926-NP在人CRC HCT116细胞中表现出强大的抗肿瘤活性。在CRC异种移植模型中，与对照组相比，用ST1926-NP治疗的小鼠在低药物浓度下肿瘤体积显著降低，并增强了ST1926向肿瘤的递送。这些发现突出了ST1926-NP在减轻CRC肿瘤生长方面的潜力，促进其在临床环境中的进一步发展。
