Researchers Jasmine Kaur and Kulbhushan Tikoo Credit: NIPER
Scientists from National Institute of Pharmaceutical Research, Mohali, have described the molecular mechanism of an RNA aptamer which specifically targets drug resistant and metastatic cancer cells1.
Aptamers – single stranded nucleic acids – have emerged as contemporaries to antibodies due to their high affinity for target cells and researchers worldwide are working on aptamer-based drug delivery systems.
The NIPER researchers selected the RNA aptamer through Cell-SELEX process. The aptamer shows high specificity towards its target gefitinib-resistant lung cancer cells and spares the normal lung cells. They used this aptamer to deliver gefitinib-loaded nanoparticles synthesised earlier2.
Aptamer conjugated geftinib nanoparticles (GNPs) showed higher internalization and retention within the resistant cell type as compared to normal GNPs. Due to this the anti-cancer activity of the bio-conjugate was also higher. They did not observe any internalization of bio-conjugate within normal lung cells and saw higher efficacy of the delivery system in xenograft mice with tumours.
“The bio-conjugate alleviates tumour growth. It also significantly lowers body weight loss in bio-conjugate treated animals as compared to animals treated with gefitinib and GNPs,” says lead researcher Kulbhushan Tikoo.
The researchers used bioinformatic approach to identify the aptamers’ target and were intrigued to find that the aptamer was identifying Ets-1, an oncogenic transcription factor, as its target. Through extensive transfection and co-localization assays, they showed that the high specificity of their aptamer towards drug resistant cells was due to the presence of high levels of Ets-1 in these cells.
Their selected aptamer also internalized within other Ets-1 expressing metastatic and drug resistant cancer cells like H23 lung cancer, MDA-MB231 breast cancer and DU-145 prostate cancer cells. The delivery system, they say, is well suited for not only carrying pharmaceutical cargoes within Ets-1 expressing metastatic cancer cells but also for the diagnosis of highly progressive cancer cells.
