A molecular octopus for capturing cancer cells

Title Regenerative NanoOctopus Based on Multivalent-Aptamer-Functionalized Magnetic Microparticles for Effective Cell Capture in Whole Blood
Author Yongli Chen, Deependra Tyagi, Mingsheng Lyu, Andrew J. Carrier, Collins Nganou, Brian Youden, Wei Wang, Shufen Cui, Mark Servos, Ken Oakes, Shengnan He, and Xu Zhang
Journal Analytical Chemistry
Year 2019

Collecting cancer cells out of a complex blood sample can be challenging, but isolating diseased cells from healthy ones is necessary for studying real cancer samples. A cancer cell circulating in the bloodstream is far more convenient to access than performing a tumor biopsy, and for this reason these circulating tumor cells are sometimes called “liquid biopsies.” A recent study describes a new probe, designed to resemble an octopus, to specifically target and grab only cancer cells from a complex mixture. With a magnetic “head” and eight DNA “tentacles,” these NanoOctopuses recognize and bind to proteins on the cell membrane and are isolated from the remaining blood with a magnet (Figure 1).

An illustration of how the nanoOctopuses are synthesized and generally how they work.
Figure 1. An overview of the NanoOctopus. (A) NanoOctopus synthesis. DNA aptamers are attached to a magnetic microparticle, creating an octopus-like shape. (B) How the NanoOctopus works. The NanoOctopuses are added to a blood sample and are pulled off with a magnet. The NanoOctopuses can be removed from the cancer cells with an enzyme called DNAase.

The DNA tentacles use probes called aptamers to bind specifically to cancer cell membranes. Aptamers are engineered out of DNA, RNA, or peptides, to bind to a specific target, such as a protein. These aptamers use DNA as the probe and are spaced out along the tentacle with DNA spacers in between.

The NanoOctopus head is comprised of a magnetic microparticle (MP), to which the tentacles are attached using the famously strong biotin-streptavidin interaction. To separate the cancer cells from the remaining blood cells, all you need is to hold a magnet to the side of the tube and rinse the rest away. The cells can be removed from the octopus by using DNAse, a protein which degrades DNA.

So, why an octopus? Previously, researchers had tried using similar aptamer probes for capturing cells from blood in microfluidic devices, but they proved to be inefficient. Instead of being captured by the DNA strands at the walls of the microfluidic channels, cells would pass through the center, treating the strands like curtains. A magnetic octopus can be added directly the blood itself and “seek out” the target cancer cells. The tentacles can hold many probes (think of them as “suckers”) to grab and strongly hold onto cells.

The researchers showed that the NanoOctopuses captured the cancer cells in complex samples efficiently using flow cytometry, which can sort cells by type (eg. cancerous vs. non-cancerous cells). They also showed that after separating the cells, the final sample of cancerous cells was 96.7 percent pure (Figure 2).

Figure 2. Capture efficiency of the NanoOctopuses. (a) The NanoOctopuses ability to capture cancer cells in the presence of Ramos cells, a different type of cell. They capture almost all of cancer cells and very few Ramos cells, even when there are more Ramos cells than cancer cells. (b) Capture efficiency of cancer cells compared to white blood cells. The inset shows flow cytometry data of the purity of the cancer cells after NanoOctopus capture. The cells are well-separated in the chart.

As a final experiment, the researchers tested the NanoOctopuses in a clinical setting, by testing the blood of leukemia patients against healthy blood donors. The NanoOctopuses successfully captured leukemia cells from the patient samples and came up empty from the healthy blood (Figure 3). They imaged the cells with fluorescence microscopy to show that there were no leukemia cells remaining in the sample after capture.

Figure 3. NanoOctopus capture of leukemia cells in real patients. The NanoOctopuses captured leukemia cells in the patients (right) and no cells in the healthy blood controls (left).

The chemistry used to synthesize the NanoOctopuses is relatively simple and widely available, so these probes could be produced and commercialized easily. Perhaps best of all, the NanoOctopuses can also be regenerated and used many times. Instead of painful and invasive biopsies, this technology could make monitoring tumors as easy as a blood draw.

Not to mention how much easier it is to sell a nanodevice based on a zoo animal, instead of “immunomagnetic cell capture.”

Images adapted with permission from Chen, Y., et. al. Anal. Chem. 2019, 91, 6, 4017–4022. Copyright 2019 American Chemical Society.

Feature image created by the author from Pixabay and other public domain images.

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