Aptamers used for targeted cancer treatment
The research, published in Angewandte Chemie, focused on improving the delivery of cis-Diamminedichloroplatinum(II) (cisplatin), which is a potent chemotherapeutic agent but is limited by significant drawbacks.
These issues include severe side effects, lack of tumour specificity and development of resistance. By creating a delivery vehicle the researchers from the University of Illinois, US believe they have overcome some of these issues.
This delivery vehicle consists of liposomes with aptamers attached. Aptamers are single-stranded oligonucleotides that target specific cells, similar to some antibodies but they are easier to prepare and scale up.
Consequently the researchers were able to formulate aptamers-conjugated cisplatin-encapsulating multifunctional liposomes. The aptamer used in the research has a high binding affinity to nucleolin (NCL), which is linked to various diseases including breast cancer.
In cell culture the aptamers were shown to target cancer cells and the liposome is then taken up by endocytosis, delivering its cargo of cisplatin into the cytoplasm.
However, even with this targeting other cells will often be affected because the markers that aptamers target are also present on non-cancerous cells in smaller numbers.
Consequently the researchers tested the possibility of inhibiting the therapeutic using the complementary DNA (cDNA) of the aptamer. This is effective because the complementary base pairing disrupts the aptamer’s target-binding confirmation.
In the researchers’ tests this inhibiting was shown to be effective. Liposomes can carry an array of drug molecules and this creates the possibility that cDNA could be used as a universal method to neutralise aptamer-based delivery systems.
The research paper can be found here.