New Approaches to Delivery systems of Drugs or Genetic Materials into Living Cells

The administration of most drugs nowadays is delivered either orally (as pills, powders or liquids) or as injections. However, during the last few decades new drugs have been developed that require more complex delivery systems because they are targeted to specific parts of the body. One of the difficulties is that many highly-effective new drug compounds do not cross the cell membrane easily. This is also true for DNA/RNA vaccines, which is a novel method to immunize humans against bacterial, viral or parasitical infections. The basic principle is that a vaccine of DNA/RNA is inserted into the host cells, thus transferring genetic information providing immunization. However, DNA/RNA is not easily transferred through the cell membrane.

To address this specific issue of transporting drug compounds or DNA/RNA into living cells the Mendeleev Chemical Technological University (Moscow) and the Department of Chemistry of the Moscow State University, under ISTC project 3175, have developed special molecules that assist in the transportation into cells.

The project team developed and synthesized amphiphilic copolymers, which are partly hydrophobic (non-water soluble) and partly hydrophilic (water soluble). The hydrophilic part is a co-polymers, i.e. the polymers has different functional groups, one group interacts well with drug or DNA/RNA fragments, wile the other group interacts well with cell membranes. These types of copolymers form nanoscale containers, called micelles, can be incorporated into bioactive additives, such as drug compounds or DNA/RNA fragments.

The project team has successfully formulated several types of amphiphilic copolymers that work with either drug compounds or DNA/RNA fragments (see pictures). Currently, the participants are looking for industrial partners to develop these copolymers on a commercial basis.

Outcome: Multiple novel amphiphilic copolymers that transfer drug compounds or DNA/RNA fragments into living cells were developed.

Microscope picture of humanbreast cancer cells (a) and fluorescence pictures of these cells incubated with fluorescence-labeled antitumor-compound doxorubicin (Dox). In the absence of copolymers (b) Dox did not penetrate into the cells. However, in the presence of different types of developed copolymers (c), (d), (e), (f) Dox uptake can be significantly increased into the cells, depending on the type of amphiphilic copolymer selected.

Fluorescence pictures of humanbreast cancer cells incubated with fluorescence labelled DNA. In the absence of copolymers (a) DNA hardly penetrates into the cells. However, in the presence of positively charged copolymers DNA penetration into the cells is significantly increased (b).

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