‘Glowing’ nanotech guides cancer surgery, kills remaining cancer cells

“If it glows, cut it out.”
January 5, 2015

A dendrimer nanoparticle (blue) carries a drug (green) into cancer cells for improved surgery and phototherapy (credit: Oregon State University)

Oregon State University researchers have developed a new way to selectively  insert compounds into cancer cells — a system that will help surgeons identify malignant tissues and then, in combination with phototherapy, kill any remaining cancer cells after a tumor is removed.

The method should allow more accurate surgical removal of solid tumors at the same time it eradicates any remaining cancer cells. In laboratory tests, it completely prevented cancer recurrence after phototherapy.

“With this approach, cancerous cells and tumors will literally glow and fluoresce when exposed to near-infrared light, giving the surgeon a precise guide about what to remove,” Taratula said. “That same light will activate compounds in the cancer cells that will kill any malignant cells that remain. It’s an exciting new approach to help surgery succeed.”

How it works

The researchers used a compound called naphthalocyanine, which has some unusual properties when exposed to near-infrared light: It can make a cell glow as a guide to surgeons; heat the cell to kill it; and produce reactive oxygen species (chemicals such as hydrogen peroxide) that can also kill a cell if the other methods don’t work. By adjusting the intensity of the light, the action of the compound can be controlled and optimized to kill just the tumor and cancer cells. This research was done with ovarian cancer cells.

Normally, naphthalocyanine isn’t water soluble and also tends to clump up, or aggregate, inside the body, in the process losing its ability to makes cells glow and generate reactive oxygen species. This also makes it difficult or impossible to find its way through the circulatory system and take up residence only in cancer cells.

OSU experts overcame these problems by use of a special water-soluble polymer, called a dendrimer, which allows the napthalocyanine drug to hide within a molecule that will attach specifically to cancer cells, and not healthy tissue. The dendrimer, an extremely tiny nanoparticle, takes advantage of certain physical characteristics that blood vessels leading to cancer cells have, but healthy ones do not. It will slip easily into a tumor but largely spare any healthy tissue.

Once in place, and exposed to near-infrared light, the cancer cells will glow, creating a biological road map for a surgeon to follow in identifying what tissues to remove and what to leave. The light exposure also activates the naphthalocyanine to kill any remaining cells.

“This is kind of a double attack that could significantly improve the success of cancer surgeries,” said Oleh Taratula, an assistant professor in the OSU College of Pharmacy.

This one-two punch of surgery and a nontoxic, combinatorial phototherapy holds significant promise, Taratula said. It’s quite different from existing chemotherapies and radiotherapies. “For many cancers, surgery is a first choice of treatment,” Taratula said. “In coming years we may have a tool to make that surgery more precise, effective and thorough than it’s been before.”

Human trials

Before attempting human clinical tests, OSU researchers hope to perfect the process and then collaborate with Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine, to test it on live dogs that have malignant tumors. The technique has already been shown successful in laboratory mice. Worth noting, the researchers said, is that even as phototherapy was destroying their malignant tumors, the mice showed no apparent side effects and the animals lost no weight.

Systems with technology similar to this are also being tested by other researchers, but some of them require several imaging and therapeutic agents, repeated irradiation and two lasers. This increases cost, may lessen effectiveness, and increases risk of side effects, OSU researchers noted in their report in the journal Nanoscale.

This research was supported by the OSU College of Pharmacy, the Medical Research Foundation of Oregon and the PhRMA Foundation.

Abstract of Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy

Multifunctional theranostic platforms capable of concurrent near-infrared (NIR) fluorescence imaging and phototherapies are strongly desired for cancer diagnosis and treatment. However, the integration of separate imaging and therapeutic components into nanocarriers results in complex theranostic systems with limited translational potential. A single agent-based theranostic nanoplatform, therefore, was developed for concurrent NIR fluorescence imaging and combinatorial phototherapy with dual photodynamic (PDT) and photothermal (PTT) therapeutic mechanisms. The transformation of a substituted silicon naphthalocyanine (SiNc) into a biocompatible nanoplatform (SiNc-NP) was achieved by SiNc encapsulation into the hydrophobic interior of a generation 5 polypropylenimine dendrimer following surface modification with polyethylene glycol. Encapsulation provides aqueous solubility to SiNc and preserves its NIR fluorescence, PDT and PTT properties. Moreover, an impressive photostability in the dendrimer-encapsulated SiNc has been detected. Under NIR irradiation (785 nm, 1.3 W cm−2), SiNc-NP manifested robust heat generation capability (ΔT = 40 °C) and efficiently produced reactive oxygen species essential for PTT and PDT, respectively, without releasing SiNc from the nanopaltform. By varying the laser power density from 0.3 W cm−2 to 1.3 W cm−2 the therapeutic mechanism of SiNc-NP could be switched from PDT to combinatorial PDT–PTT treatment. In vitro and in vivo studies confirmed that phototherapy mediated by SiNc can efficiently destroy chemotherapy resistant ovarian cancer cells. Remarkably, solid tumors treated with a single dose of SiNc-NP combined with NIR irradiation were completely eradicated without cancer recurrence. Finally, the efficiency of SiNc-NP as an NIR imaging agent was confirmed by recording the strong fluorescence signal in the tumor, which was not photobleached during the phototherapeutic procedure.