Huang, Bo-TsangBo-TsangHuangLai, Wei-YunWei-YunLaiYeh, Chen-LinChen-LinYehTseng, Yi-TingYi-TingTsengPeck, KonanKonanPeckPAN-CHYR YANGLin, Emily Pei-YingEmily Pei-YingLin2024-11-112024-11-112024-10-15https://scholars.lib.ntu.edu.tw/handle/123456789/722954Treatment of lung cancer leptomeningeal carcinomatosis (LM) remains challenging partly due to the biological nature of the blood-brain barrier (BBB). Cisplatin has limited effects on LM, and it is notorious for neurotoxicity. Aptamers are small oligonucleotides considered as antibody surrogates. Here we report a DNA therapeutics, AptBCis1. AptBCis1 is a cisplatin-conjugated, BBB-penetrating, and cancer-targeting DNA aptamer. Its backbone, AptB1, was identified via SELEX using lung cancer LM orthotopic mouse models. The AptB1 binds to EAAT2, Nucleolin, and YB-1 proteins. Treatment with AptBCis1 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) showed superior tumor suppressive effects compared to cisplatin 2 mg/kg in mice with lung cancer LM diseases. The cerebrospinal fluid platinum concentration in the AptBCis1 group was 10% of that in the cisplatin group. The data suggested the translational potential of AptBCis1 in lung cancer with LM and in cancers in which platinum-based chemotherapy remains as the standard of care.enaptamerblood−brain barriercisplatinin vivo SELEXleptomeningeal carcinomatosislung cancerjournal article10.1021/acsnano.4c0468039360769