MIT chemical engineers have developed a new sensor that allows them to see inside cancer cells and determine whether the cells respond to a certain type of chemotherapy drug.
Sensors that detect hydrogen peroxide in human cells may help researchers identify new drugs for cancer which increase the level of hydrogen peroxide, which induces programmed cell death. The sensors may also be adapted for screening for tumors of individual patients to predict whether such preparations are effective against them.
"The therapy will not work against all tumors", - said Hadley Sikes, associate professor of chemical engineering at MIT. "Currently, there is a real lack of quantitative, chemical specific tools to measure changes in tumor cells compared to normal cells in response to treatment."
Sykes is a senior author of the study, which appeared in Nature Communications release of August 7. The first author of the article - a graduate student Troy Langford; Other authors - former graduate students of Beijing Huang and graduate student Joseph Lim and San Jin Moon.
Monitoring of hydrogen peroxide
Cancer cells often have mutations that cause them to be digested and metabolism produce abnormally high fluxes of hydrogen peroxide. When formed too big portion of the molecule, it can damage cells, cancer cells so strongly depend on antioxidant systems which remove hydrogen peroxide from the cells.
Drugs that target this vulnerability, which are known as "redox drugs", can be operated either by switching off the antioxidant systems, any further increase in production of hydrogen peroxide. Many of these drugs have entered clinical trials, with mixed results.
"One problem is that clinical trials often find that they work for some patients, and they do not work for the other patients," - says Sykes. "We really need the tools to be able to conduct more well-designed trials, when we find out which patients will respond to this approach, and what does not, so more of these drugs can be approved."
To help move towards this goal, Sykes decided to develop a sensor that could sensitively detect hydrogen peroxide in human cells, allowing scientists to measure the cell response to these drugs.
Existing detectors of hydrogen peroxide based on proteins called transcription factors taken from microbes and designed to fluorescence when they react with hydrogen peroxide. Sikes and her colleagues tried to use them in human cells, but found that they are not sensitive in the range of hydrogen peroxide, which they tried to find out what made them look human proteins that could perform this task.
Through research network human proteins that are oxidized with increasing hydrogen peroxide, researchers have identified an enzyme called peroxiredoxins which dominates in most reactions of human cells with a molecule. One of the many functions of this enzyme is to determine changes in the levels of hydrogen peroxide.
Langford protein is then modified by adding to it two fluorescent molecules - green fluorescent protein at one end and red fluorescent protein to the other end. When the sensor reacts with hydrogen peroxide, its shape changes, the two fluorescent protein converging. Researchers can determine whether this shift occurred when glow green light on the cells: if hydrogen peroxide is not detected, the glow remains green; If hydrogen peroxide is present, instead the sensor is lit red.
Researchers tested a new sensor in the two types of human cancer cells: one set, which they knew was sensitive to redox drugs called piperlonguminom, and the other, which they knew was not receptive. The sensor showed that the levels of hydrogen peroxide is not changed in the resistant cells, but were increased in susceptible cells, researchers expected.
Sykes provides two main applications of this sensor. One is the study of existing drugs or compounds that could potentially be used as drugs to determine if they have the desired effect of increasing the concentration of hydrogen peroxide in cancer cells. Another potential use is to screen patients before they receive these drugs to see whether successful drug against each patient's tumor. Currently, Sykes pursues both of these approaches.
"You should know what cancer drugs work this way, and then some of the tumor will react", - she says. "These are two separate but related issues that must be addressed to this approach has practical implications in the clinic."