23 December 2021

Doxorubicin in nanopackage

Glioblastoma is considered the most aggressive brain tumor. Even with timely treatment, survival remains low, and most of the patients live an average of 15-18 months after diagnosis. Due to the large spread of glioblastoma characteristics and localization in a well-protected organ, the treatment of this disease is a difficult task.

A new drug delivery system based on nanotechnology, created by a group of bioengineers from the Universities of Minnesota and Johns Hopkins, is able to improve survival rates by accurately targeting the primary tumor.

The main obstacle preventing drugs from entering brain tumors through the bloodstream is the blood–brain barrier (BBB), which is necessary to protect the brain from toxins, but can also block drug molecules. Using nanotechnology, the group created a single-stranded DNA (ssDNA) capable of passing through the BBB. A self-assembled nanotube was created from ssDNA and other molecules, which can carry therapeutic drugs.

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To test the accuracy of the delivery of antitumor "cargo" by ssDNA nanotubes, the researchers injected them into both hemispheres of the mouse brain: one hemisphere was healthy, and the second was affected by glioblastoma. Nanotubes accumulated in tumors, but were absent on the healthy half of the brain, which indicates the safety of the new delivery method for healthy cells. When nanotubes were inserted into a vein on the tail of animals, the results were the same. This proves that they have successfully passed through the BBB and reached the brain.

Complete surgical removal of glioblastoma is not possible, since it is a multiple tumor, and traces of cancer cells may remain, causing a relapse. Therefore, after surgery, patients receive a course of chemotherapy. As part of their study, the team evaluated nanotubes as a means of delivering the chemotherapeutic drug doxorubicin. To do this, mice were injected with glioblastoma cells to simulate residual cancer cells after tumor resection. After that, an infusion pump was implanted into the rodents' brains for various procedures. Some mice received "empty" nanotubes, while others received doxorubicin directly into brain tissue or using DNA nanotubes.

The treatment lasted two weeks, the mice were monitored for about a month and a half. Mice that received doxorubicin in nanotubes showed an increase in survival: half of them survived to the end of the study. It is noteworthy that mice directly treated with doxorubicin suffered from toxic damage to the liver and spleen. On the contrary, no significant changes were found in the tissues of the spleen and liver of mice injected with nanotubes without a load and with doxorubicin.

The results showed that ssDNA nanotubes are a promising tool for delivering antitumor molecules to brain tumors.

The article by M.A.Harris et al. ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival is published in the journal Science Advances.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Johns Hopkins University: DNA nanotubes deliver therapeutics to glioblastoma tumors.

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