Nanoparticles for the treatment of drug-resistant forms of cancer
Northeastern University scientists dealing with the problems of multidrug resistance of cancer tumors, in collaboration with the Nanotechnology Alliance of the National Cancer Institute, have developed polymer nanoparticles that first deliver a strong anti-cancer drug directly to cancer cells, and then release an agent that initiates spontaneous death processes in drug-resistant cells.
Testing of a new type of therapy on a human tumor (breast cancer) vaccinated in mice showed effective achievement of high concentrations of both agents in close proximity to the tumor. These agents are the previously developed anticancer agent paclitaxel (paclitaxel) and the cell death-initiating ceramide (ceramide).
Paclitaxel is an antitumor drug of plant origin that prevents the formation of a mitotic spindle of dividing cells. Ceramide is a lipid component of the membrane, which is also a signaling molecule and causes apoptosis (programmed cell death) in cases of cell damage or disruption of the cell cycle.
The results of the work conducted under the leadership of Mansoor Amiji were recently published in the journal Molecular Pharmaceuticals (Biodistribution and Pharmacokinetic Analysis of Paclitaxel and Ceramide Administered in Multifunctional Polymer-Blend Nanoparticles in Drug Resistant Breast Cancer Model).
In the study, these two drugs were placed in nanoparticles consisting of two polymers. The first polymer, poly(beta-aminoester), PbAE, rapidly dissolves in an acidified medium inside the tumor cell, releasing paclitaxel. The second polymer, poly(d,l-lactide-co-glycoside), PLGA dissolves under the same conditions more slowly, releasing ceramide in the phase when changes have already occurred in the cancer cell and resistance has formed, and when the cell is ready to enter apoptosis. It is known that resistant tumor cells are able to lower the natural concentration of ceramide, destroying its molecules, so additional ceramide helps the natural process.
In a mouse model of human breast cancer using these nanoparticles, scientists measured the concentration of drugs in the blood and in the immediate vicinity of the tumor. A mixture of two types of nanoparticles excellently maintained a high level of drugs in the body of mice, and their release and accumulation were observed in the tumors themselves. In this study, the task was not to identify the therapeutic effect, the study of which will be devoted to further work.
Maria Kostyukova, Nanonews Network Portal "Eternal youth" www.vechnayamolodost.ru