Scientists have improved the anti-cancer chemotherapy drug, cisplatin, owing to aptamers and the polymer arabinogalactan. The modification allowed targeted delivery of the drug to the tumor, significantly reducing its therapeutic dose and toxicity, but at the same time increasing its effectiveness. Researchers believe that this therapy will improve the quality of life of patients. The results of the study are published in the journal Nucleic Acid Therapeutics.

Cisplatin is an effective drug for the treatment of various types of cancer, especially in their early stages. However, it is highly toxic not only for tumor cells, but also for healthy ones. Due to its non-specificity, the drug circulates throughout the body and causes serious side effects. According to the literature, 90% of cisplatin binds to plasma proteins, 8% is distributed between organs and causes toxic effects at the body level, for example, impaired renal function, leukopenia, thrombocytopenia, neuropathy. Only about 2% of this chemotherapy drug penetrates the tumor tissue, directly destroying the cancer cells. For a safer and more targeted effect, targeted delivery of cisplatin to tumor cells is required, which will reduce its therapeutic dose and toxicity.

Scientists of the Federal Research Center KSC SB RAS, V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University and Siberian Federal University, together with colleagues from Canada, have developed a complex of an aptamer and an antitumor drug for successful and less toxic treatment of cancer diseases.

The new drug is a hybrid molecule created from the chemotherapy drug cisplatin coated with a biodegradable polysaccharide from Siberian larch, namely, arabinogalactan. Arabinogalactan protects the body cells from the toxic effects of this poison. Targeted drug delivery to tumor formations was performed using an aptamer, a short DNA molecule highly specific to Ehrlich’s ascites carcinoma cells, taken as an aggressive tumor model. The resulting drug was tested on mice with ascites, solid and metastatic forms of Ehrlich's carcinoma.

Studies showed that polymer coating in combination with targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity. At the same time, the drug suppressed the growth of Ehrlich's ascites carcinoma and reduced the degree of its metastasis by a factor of three. Arabinogalactan and aptamers increase the effectiveness of the original anticancer drug by increasing its bioavailability and targeted action on tumor cells. The developed complex can become a promising tool for antitumor therapy.

“Most of the free cisplatin in the bloodstream is immediately taken up by plasma proteins, so it reduces its effectiveness before it reaches cancer cells. A protective coating of arabinogalactan in combination with targeted delivery can reduce the toxicity of cisplatin and increase its accumulation in tumor tissue. In the developed complex, the cisplatin dose was reduced by 15 times. At the same time, we observed a pronounced antitumor effect with virtually no toxic side effects. No death of experimental animals, loss of body weight, activity or hair were observed. The reason for this phenomenon is that arabinogalactan and the aptamer promote targeted delivery of cisplatin to the tumor. Arabinogalactan enters the cell through lectin receptors, which are not found in all organs, and carries cisplatin. This partial selectivity reduces the effective dose of cisplatin. The aptamer further increases the specificity, brings the arabinogalactan-cisplatin complex directly to the cancer cell. This approach can increase survival and improve the patients' quality of life and life expectancy by reducing the drug toxicity and side effects. Thus, the developed complex makes it possible to reduce the doses of toxic drugs while maintaining the therapeutic effect, ” said Anna Kichkaylo, Doctor of Biology, Head of the Laboratory of Digital Controlled Drugs and Theranostics of FRC KSC SB RAS, Head of the Laboratory of Biomolecular and Medical Technologies of the V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University.