AptBCis1, An Aptamer–Cisplatin Conjugate, Is Effective in Lung Cancer Leptomeningeal Carcinomatosis

• Published in: ACS nano 2024-10, Vol.18 (41), p.27905-27916
• Main Authors: Huang, Bo-Tsang, Lai, Wei-Yun, Yeh, Chen-Lin, Tseng, Yi-Ting, Peck, Konan, Yang, Pan-Chyr, Lin, Emily Pei-Ying
• Format: Article
• Language: English
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/acsnano.4c04680

Treatment 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 in vivo 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.