Nanoprobes hit targets in tumors, could lessen chemo side effects
A variety of nanoparticles have shown to be effective in delivering cancer drugs more directly to tumor cells, mitigating the damage to nearby healthy cells. Now, researchers from Purdue University have demonstrated that these nanoparticles are getting their drug payloads to the correct intracellular compartments.
Joseph Irudayaraj, Ph.D., and graduate student Jiji Chen have found that gold nanorods coated with the breast cancer drug Herceptin are reaching the endosomes of cells, mimicking the delivery of the drug on its own. Endosomes perform a sorting function to deliver drugs and other substances to the appropriate locations.
"We have demonstrated the ability to track these nanoparticles in different cellular compartments of live cells and show where they collect quantitatively," said Dr. Irudayaraj, whose results were published in the journal ACS Nano. "Our methods will allow us to calculate the quantities of a drug needed to treat a cancer cell because now we know how these nanoparticles are being distributed to different parts of the cell."
The nanoprobes used in this study are made from gold and magnetic particles. An MRI scanner can track the magnetic portions of the nanoprobes while a more sensitive microscopy process known as fluorescence correlation spectroscopy, which is capable of detecting single molecules, can spot the gold. The nanoprobes were inserted into live human tumor cells during laboratory testing. Using fluorescent markers to differentiate organelles, or sub-units of cells, Dr. Irudayaraj and his graduate student were able to determine the number of nanoprobes accumulating in the endosomes, lysosomes and membranes of those cells.
In this study, endosomes received a major portion of the nanorods containing Herceptin. Lysosomes, which act like garbage collection units in cells and hinder a drug's effectiveness, received a lower concentration of nanorods. Dr. Irudayaraj said those percentages are similar to how cells distribute drugs through traditional treatments. He will next try to attach multiple drugs to a nanoparticle and track their distribution within cells. He also wants to determine the timing of a drug's release from the nanoprobes after attaching to the tumor cells.
This work is detailed in a paper titled, "Quantitative investigation of compartmentalized dynamics of ErbB2 targeting gold nanoparticles in live cells by single molecule spectroscopy." An abstract of this paper is available on the journalís Web site.