Physicists Have a New Way of Precision Targeting Cancer Cells

The perils of cancer treatment are well known: To target the bad cells, it's usually necessary to hit some of the good ones in the process. Friendly fire.

Cancer cells are just so often deeply integrated within healthy tissues, sharing not just space with normal cells, but characteristics, too. Conventional chemotherapeutic agents are cytotoxic to cells that are fast-reproducing, which includes cancer cells by definition, but also lots of healthy cells as well. Radiation therapy, meanwhile, involves firing intersecting beams of destructive radiation at tumors—hitting some neighboring healthy cells in the process, to varying degrees, is part of the bargain.

Researchers are aggressively hunting for alternatives capable of targeting cancer cells at the highest possible resolutions. A therapeutic agent capable of softly knocking on the door of a cancer cell in the middle of the night and hustling it away in an unmarked van is a long-sought capability. To that end, physicists at the Niels Bohr Institute at the University of Copenhagen have accomplished something very close: a molecular "vehicle" with the ability to deliver a cytotoxic agent directly to a cancer cell, and then prompt that cancer cell—and only the cancer cell—to accept the destructive payload. The Copenhagen group's research is described this week in the journal Scientific Reports.

The idea is pretty clever. Again: Chemotherapy involves dumping a bunch of cytotoxic chemicals into the body more or less as-is, which then go on to kill fast-reproducing cells, healthy or no. What the physicists imagined is a cytotoxin that would only be accepted into a cell under certain conditions. What if it was, say, bundled in with something that cancer cells really want?

The question was then of what that thing could be. Noting that cancer often spreads to the bones, the physicists decided to try pairing the cytotoxic Paclitaxel (PTX), a popular and effective drug used to treat lung, breast, and ovarian cancers, with a variety of calcium phosphate called hydroxyapatite (HAP), a mineral required for bone growth and health.

"The use of [HAP], the main inorganic constituent of human bones and teeth, is an excellent candidate," the physicists note. "At the nano-scale, HAP presents special biocompatibility as well as non-immunogenicity, non-inflammatory behaviour, high osteoconductivity, and good adhesion to different types of cancer cells. Of even more interest, HAP nanoparticles (nHAP) show inhibitory effect on cancer cells proliferation with lower effects on the healthy ones."

Tiny, cell-scale units of cytotoxins were first doped with even tinier magnetic beads, a common technique in medical research useful for driving substances around the body or around tissues using magnets. These units were then coated with a protective layer of a biological polymer material, leaving capsules of encapsulated poison protected from their surroundings (and vise versa). These capsules were then doped with HAP particles.

In experiments with breast cancer, lung cancer, and colon cancer cells, the group found that their cytotoxic payloads were being ignored by healthy cells and accepted into cancer cells. The cancer cells showed evidence of metabolic changes and the early stages of cell death. It was working.

"The next steps in this work will focus on further understanding the encapsulation effects on the dynamics of the released PTX and its correlation with its biological activity as well as in the optimization of the drug release mechanism," the researchers conclude.

Using calcium phosphate as a cancer-targeting agent isn't an entirely new idea. It's been suggested a few times in recent years, albeit with different mechanisms. For one thing, the mineral is known to break down in the acidic microenvironment of tumors, leaving open the possibility of delivering cytotoxins within calcium phosphate containers that open up on the doorstep of cancer cells, but not healthy cells. In the currently proposed scheme, the mineral acts more as a happy wrapping paper around the toxin with some other biologically useful polymer forming the box (a ring-shaped sac, really), while the earlier alternative would use the mineral as the box itself.

The trick with encapsulating cytotoxins is that they don't always properly couple to their container, leaving the possibility of still introducing a bunch of unprotected, dangerous cytotoxins into the patient. Part of the Copenhagen group's advance was in developing a screening system to separate out the uncoupled cytotoxins from the properly sealed cytotoxins.

This isn't a cure for cancer, but it does at least promise a new way around the toxic effects of chemotherapy treatments. That's good for general patient well-being, but we can also imagine it opening up new and possibly more effective chemotherapy dosage ranges, or perhaps opening up the possibility of treatment at all for patients otherwise too weak or sick to withstand it.