Gold-plated nano-bits find, destroy cancer cells.

Carl Batt

Dickson Kirui


Comparable to nano-scale Navy Seals, Cornell scientists have merged tiny gold and iron oxide particles to work as a team, then added antibody guides to steer the team through the bloodstream toward colorectal cancer cells. And in a nanosecond, the alloyed allies then kill the bad guys – cancer cells – with absorbed infrared heat.

This scenario is not science fiction – welcome to a medical reality.

“It’s a simple concept. It’s colloidal chemistry. By themselves, gold and iron-oxide alloys are benign and inert, and the infrared light is low-power heating,” said Carl Batt, Cornell’s Liberty Hyde Bailey Professor of Food Science and the senior author on the paper. “But put these inert alloys together, attach an antibody to guide it to the right target, zap it with infrared light and the cancer cells die. The cells only need to be heated up a few degrees to die.”

Batt and his colleagues – Dickson K. Kirui, Ph.D. ’11, a postdoctoral fellow at Houston Methodist Research Institute and the paper’s first author; Ildar Khalidov, radiology, Weill Cornell Medical College; and Yi Wang, biomedical engineering, Cornell – published their study in Nanomedicine (print edition, July 2013).

For cancer therapy, current hyperthermic techniques – applying heat to the whole body – heat up cancer cells and healthy tissue, alike. Thus, healthy tissue tends to get damaged. This study shows that by using gold nanoparticles, which amplify the low energy heat source efficiently, cancer cells can be targeted better and heat damage to healthy tissues can be mitigated. By adding the magnetic iron oxide particles to the gold, doctors watching MRI and CT scanners can follow along the trail of this nano-sized crew to its target.

When a near-infrared laser is used, the light penetrates deep into the tissue, heating the nanoparticle to about 120 degrees Fahrenheit – an ample temperature to kill many targeted cancer cells. This results in a threefold increase in killing cancer cells and a substantial tumor reduction within 30 days, according to Kirui. “It’s not a complete reduction in the tumor, but doctors can employ other aggressive strategies with success. It also reduces the dosage of highly toxic chemicals and radiation – leading to a better quality of life,” he explained.

Cornell dots show promise in targeting cancer cells during surgery.

The U.S. Food and Drug Administration (FDA) has approved the first clinical trial of a new technology that uses radiolabeled nanoparticles to brighten cancer cells so they can be detected by a PET-optical imaging camera.

Researchers from Memorial Sloan-Kettering Cancer Center (MSKCC) and Cornell University are collaborating with Hybrid Silica Technologies, a Cornell start-up company, and Dutch optical imaging developer O2view on the project and clinical trial.

The FDA’s investigational new drug (IND) approval for the study represents the first inorganic particle platform of its class to be used for multiple clinical indications, according to co-researcher Dr. Michelle Bradbury, a neuroradiologist at MSKCC and assistant professor of radiology at Weill Cornell Medical College.

The trial will explore the applications of cancer targeting and future therapeutic diagnostics, as well as cancer disease staging and tumor burden assessment through lymph node mapping.

Multiple applications

“Cancer has largely been the heavy hitter for nanoparticle probes, and I think there are overlaps with other diseases where institutions could make use of such types of particles,” Bradbury “We are developing the [therapeutic diagnostic] probes and using them for surgical applications, mainly lymph node mapping.”

The so-called “Cornell dots” are silica spheres approximately 6 nm in diameter that enclose several dye molecules. The silica shell, which is essentially glass, is chemically inert and small enough to pass through the body and exit in the urine. For clinical applications, the dots are coated with neutral molecules — polyethylene glycol (PEG) — so the body will not recognize them as foreign substances and activate a patient’s immune system to reject them.

To make the nanoparticles adhere to tumor cells, organic molecules that bind to tumor surfaces or specific locations within tumors can be attached to the PEG shell. When exposed to near-infrared light, the dots become brighter and help identify the targeted cancer cells.

Nanoparticle half-life

Nanoparticles in general can linger in the bloodstream for many hours and even days, depending on their size. Given their 6-nm size, the nanoparticles have a half-life of approximately six hours in the bloodstream before evacuation through the kidneys. “Within a 24-hour period,” Bradbury said, “50% may be cleared through the kidneys.”

Among the researchers’ goals in this trial is to validate the pharmacokinetics and dosimetry of the nanoparticles and PET-optical imaging technology for safe use in humans. Researchers also will collect blood and urine samples to see how different parts of the body, besides organs, react to the nanoparticles.

The study will include five metastatic melanoma patients as its first enrollees. “If all goes well with a few patients, we hope to proceed with a targeted study,” Bradbury said.

Surgical information

The technology, the researchers believe, could be particularly beneficial during surgical treatment, allowing surgeons to see the invasive or metastatic spread to lymph nodes and distant organs and illustrating the extent of treatment response.

Initially, the surgical applications will include cancer within the complex area of the head and neck. With the help of the nanoparticles and PET-optical imaging camera, surgeons will be able to detect the activity of the lymph nodes.

Currently, Bradbury explained, physicians have little or nothing to refer to during surgery other than a preclinical scan — and compared to the scan, the patient is now in a totally different position on the table.

“How would they know where they are in the neck?” she asked. “They just don’t [know], so they want tools so they can see what they are doing and see the nodes in relation to vital structures, such as nerves. They don’t want to pick up activity from a lymph node plus an adjacent tumor, which would be easy to do, if you don’t know where you are exactly.”

Nanoparticles in mice

Researchers have already had some success with the nanoparticles and the PET-optical imaging technology in a preclinical study in mice. Among the conclusions is that the nanoparticles have been “optimized for efficient renal clearance” and “concurrently achieved specific tumor targeting” (Journal of Clinical Investigation, July 2011, Vol. 121:7, pp. 2768-2780).

In addition, the multimodal silica nanoparticles exhibit “what we believe to be a unique combination of structural, optical, and biological properties,” wrote lead study authors Dr. Miriam Benezra and Dr. Oula Penate-Medina and colleagues.

To be clinically successful, the group added, the “next generation of nanoparticle agents should be tumor selective, nontoxic, and exhibit favorable targeting and clearance profiles. Developing probes meeting these criteria is challenging, requiring comprehensive in vivo evaluations.”