AptBCis1, An Aptamer-Cisplatin Conjugate, Is Effective in Lung Cancer Leptomeningeal Carcinomatosis.
Journal
ACS nano
Journal Volume
18
Journal Issue
41
Start Page
27905
End Page
27916
ISSN
1936-086X
Date Issued
2024-10-15
Author(s)
Abstract
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 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.
Subjects
aptamer
blood−brain barrier
cisplatin
in vivo SELEX
leptomeningeal carcinomatosis
lung cancer
Type
journal article