Ball Bomb for Ovarian Cancer
Nanoparticles carrying nanoliposomes with miRNA,
reduce the mass of ovarian cancers by 83 percent
LifeSciencesToday based on the materials of The Methodist Hospital: Nanotech'ed RNA drug reduces ovarian cancer tumors by 83 percentBy enclosing unstable miRNA in silicon nanoparticles, scientists at The Methodist Hospital, in collaboration with two other US research centers, have obtained a new drug delivery system capable of reducing the size of ovarian cancer tumors by as much as 83 percent and stopping the growth of tumors in chemotherapy-resistant tissue.
The most interesting results of a study conducted on animal models are published in the journal Clinical Cancer Research (Shen et al., Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery).
"Resistance to drug therapy is a huge clinical problem," explains Mauro Ferrari, PhD, one of the leaders of the work. "Our work shows that longer-term protection of RNA, allowing it to get to where it should and perform its function inside cancer cells, not only enhances the effect of the RNA itself, but also restores sensitivity to traditional cancer drugs to cancer cells resistant to chemotherapy."
According to the forecasts of the US National Cancer Institute, ovarian cancer will be diagnosed, at one age or another, in every seventy-second of women born today. Mortality from this type of cancer largely depends on how early the disease is diagnosed, and ranges from 8.5 to 78 percent. One of the main reasons for the failure of chemotherapy in the fight against this disease is drug resistance.
This work combines nanoparticle production technologies independently developed by The Methodist Hospital Research Institute and the Anderson Cancer Center at the University of Texas. (The University of Texas MD Anderson Cancer Center).
"In order to increase the survival rate of cancer patients, new approaches to overcoming drug resistance are urgently needed, and in this regard, small interfering RNAs are very promising," says co–director of the study Anil Sood, MD, (Department of Gynecological Oncology and Reproductive Medicine of the Anderson Center).
Dr. Sud and his colleague Gabriel Lopez-Berestein, MD, have developed an approach to the treatment of ovarian cancer based on the use of miRNA.
Small interfering RNAs, or miRNAs (small inhibitory RNA, siRNA), are fragments of genetic material that suppress the expression of genes, in this case, one of the most important genes associated with the development of ovarian cancer – EphA2. miRNA can be used as a drug that stops the growth of cancer cells and, ultimately, killing them.
For all their safety, it makes no sense to inject miRNA into the patient's body by traditional methods: there are enzymes in the blood and inside the cells that will destroy miRNA before the molecules reach their targets – cancer cells. American scientists have created a protective shield for them – a lipid nanoparticle carrier - a nanoliposome.
miRNAs protected by liposomes cope with their task more successfully – they reach the cancer cells that absorb them – but the age of liposomes in the blood is short and they need a more reliable delivery system.
"The use of miRNA is an attractive strategy for cancer treatment, since the miRNA targets are the genes most important for the survival of cancer cells," says Haifa Shen, MD, PhD, lead author of the article. "But to overcome many biological barriers, they need an effective means of delivery. Our multi-stage vector serves as a bridge between engineering development and clinical use."
Dr. Ferrari's group has developed disc-shaped silicon nanoparticles (1 micron in diameter) designed to bind to tumor cells. Earlier work by Ferrari and his colleagues helped scientists improve the shape of particles, their size and surface chemistry, so that they specifically bind to proteins overexpressed on the surface of cancer cells.
miRNAs "packed" into liposomes embedded in the pores of silicon nanoparticles have a remarkable effect on ovarian cancer in a mouse model.
"Loading liposomes into nanoparticles not only allows targeted delivery to the tumor, but also adds another layer of protection to the miRNA," explains Dr. Shen.
miRNA–carrying nanoliposomes (yellow) are released from silicon nanoparticles (gray) near their targets - cancer cells (not shown in the figure). Intravenous injections of microscopic drug delivery systems to model animals resulted in a reduction in the weight of ovarian tumors in the range of 36-83 percent, depending on the dose. (Photo: Haifa Shen and Mauro Ferrari)
Twelve injections of 5, 10 or 15 micrograms of nanoparticles for 6 weeks resulted in a 36, 64 and 83 percent reduction in the weight of ovarian cancers, respectively, in each of the three groups of animals compared with the placebo control. In addition, a decrease in the number of tumor nodes was observed in each of the three groups.
The introduction of nanoparticles in parallel with the first- and second-line drug paclitaxel made it possible to achieve zero tumor growth.
In addition, the scientists studied the effect of miRNA-loaded nanoparticles in combination with the drug docetaxel (used in the late stage of cancer) on the tissue of ovarian cancer with multidrug resistance. Cancer cells in this group were resistant to docetaxel treatment as a monopreparation. Previous studies have shown that indirectly the resistance of ovarian cancer cells is due to the overexpression of the EphA2 gene.
"We can completely eliminate tumor nodes, which means that it is possible to achieve long–term survival of our mouse patients," Dr. Shen comments on the results of these experiments.
To assess the safety of nanoparticles with liposome-packed miRNAs, the researchers compared the body weight loss of mice in various experimental groups and found that the nanoparticles were no more toxic to animals than treatment with paclitaxel or docetaxel alone in clinically significant doses.
The next stage of the work of American scientists will, of course, be the promotion of their development in the clinic.
"We will establish contact with the FDA to develop a roadmap for clinical trials," Dr. Shen sums up.
Portal "Eternal youth" http://vechnayamolodost.ru15.02.2013